ASCO Guidelines podcast

Konten disediakan oleh Brittany Harvey and American Society of Clinical Oncology (ASCO). Semua konten podcast termasuk episode, grafik, dan deskripsi podcast diunggah dan disediakan langsung oleh Brittany Harvey and American Society of Clinical Oncology (ASCO) atau mitra platform podcast mereka. Jika Anda yakin seseorang menggunakan karya berhak cipta Anda tanpa izin, Anda dapat mengikuti proses yang diuraikan di sini https://id.player.fm/legal.

Symptomatic: A Medical Mystery Podcast

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Case #28: Ian 47:46

12 hari yang lalu47:46

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47:46

Ian Stedman suffered 32 years with full body rashes, debilitating headaches, joint pain and hearing loss without a clear diagnosis. His Mother Barb had gone over 60 years with the same symptoms. After hundreds of doctors visits and decades of frustration - they had resigned to believe there were no answers. That is until Ian’s daughter, Lia was born covered in that all-too-recognizable rash. Ian re-ignited his search for answers in an effort to save his family. We want to hear from you! Share your own medical mystery or tell us about the episode you connected with the most at Symptomatic@iheartmedia.com or drop us a voice note at https://www.speakepipe.com/symptomatic DISCLAIMER: By submitting your voice note using the link provided, you acknowledge that we have permission to potentially include that audio in future content. * * * * * * ****** SPOILER ALERT BELOW ****** You can learn more about the Canadian Autoinflammatory Network at www.autoinflammatory.ca SickKids CA can be found online at www.sickkids.ca See omnystudio.com/listener for privacy information.…

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Explore pivotal recommendations from the latest evidence-based clinical practice guidance with ASCO Guidelines. Join us to discover essential insights and navigate the ever-evolving landscape of cancer research and treatment.

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ASCO Guidelines

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Management of Antineoplastic Extravasation: ONS-ASCO Guideline 13:28

10 weeks yang lalu13:28

13:28

Dr. Tanya Thomas and Dr. Aparna Jotwani join the podcast to discuss the new Oncology Nursing Society and American Society of Clinical Oncology evidence-based guideline on the management of antineoplastic extravasation. They discuss recommendations from the expert panel on: management of extravasation of vesicant or irritant with vesicant properties antineoplastic agents, management of extravasation of paclitaxel or docetaxel, use & duration of thermal compress, and escalation of care. They share the importance of this comprehensive interdisciplinary guideline, highlight the algorithm as a useful tool for clinicians, and outline the outstanding questions related to the management of extravasation. Read the full guideline, "ONS/ASCO Guideline on the Management of Antineoplastic Extravasation" at www.asco.org/supportive-care-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/supportive-care-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the JCO Oncology Practice , https://ascopubs.org/doi/10.1200/OP-25-00579 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts . My name is Brittany Harvey, and today I'm interviewing Dr. Tanya Thomas, clinical chair of the guideline and clinical nurse specialist from University of Virginia Health, and Dr. Aparna Jotwani, medical oncologist from Baylor College of Medicine, authors on " Management of Antineoplastic Extravasation: Oncology Nursing Society – American Society of Clinical Oncology Guideline ." Thank you for being here today, Dr. Thomas and Dr. Jotwani. Dr. Aparna Jotwani: Thank you. Dr. Tanya Thomas: Thank you for having us. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Thomas and Dr. Jotwani, who have joined us here today, are available online with the publication of the guideline in JCO Oncology Practice , which is linked in the show notes. So then to dive into the content here, Dr. Thomas, could you start us off by providing an overview of both the scope and the objectives of this guideline? Dr. Tanya Thomas: Yes, so the objective of this guideline is to provide the evidence-based recommendations to help support our interdisciplinary teams, including the oncologist, the advanced practice providers, pharmacists, and nurses who are involved in the care and management of patients who are experiencing an extravasation of an antineoplastic agent. While rare, the antineoplastic and certain chemotherapy extravasations are oncologic emergencies. The recommendations are to minimize negative consequences and provide a standardized approach to the care when such an event occurs. Dr. Aparna Jotwani: I would add that our scope is limited to intravenous antineoplastic vesicants, irritants, and irritants with vesicant potential. The scope of the guideline applies to the care team for adult oncology patients receiving treatments through venous access. Outside the scope is management of extravasation during other routes of treatment administration, such as intraperitoneal, intravesical, and hepatic arterial infusion. Our recommendations regarding vascular access for therapy or interventions to prevent extravasations are also outside of the scope for this guideline. Brittany Harvey: Understood. I appreciate that background and understanding what's in scope and what's out of scope for this guideline. So then I'd like to pivot and talk about the key recommendations of this guideline across the clinical questions. So first, Dr. Jotwani, what does the panel recommend for patients with extravasation of vesicant or irritant with vesicant properties antineoplastic agents? Dr. Aparna Jotwani: The panel strongly recommends for all classes where an antidote exists to proceed with using the antidote. Recommendations for paclitaxel and docetaxel are specifically addressed in a recommendation. This is further detailed in Tables 1 and 4 within the guideline. Evidence on the use of antidotes for extravasation is limited to nonrandomized, uncontrolled, observational studies and case series. Placebo-controlled trials on this topic would be unethical. There is also a lack of comparative data for different antidote strategies. However, potential benefits of using the antidotes include tissue preservation and avoiding tissue necrosis. In developing the guidelines, we had an in-person roundtable discussion and weighed risks and benefits to ensure patient safety above all else. Brittany Harvey: I appreciate that description of the recommendation here. So then you just mentioned that there's a specific recommendation for paclitaxel and docetaxel. So what is recommended for those patients with extravasation of paclitaxel or docetaxel? Dr. Aparna Jotwani: So here, we conditionally recommended the specific use of hyaluronidase as the antidote. This was based on five studies that all used hyaluronidase as an antidote to lower the risk of tissue necrosis. In the studies included, with a subgroup of patients that experienced taxane-related extravasation, development of necrosis ranged from 0% to 0.83% among the patients who received an antidote. The potential harms associated with this were likely trivial. Brittany Harvey: Thank you for providing that recommendation as well. So then the next section of the guideline, Dr. Thomas, what does the expert panel recommend for use and duration of thermal compress? Dr. Tanya Thomas: So the expert panel actually recommends the use of thermal compresses, and the recommendations are based on the available literature for the various agents and the actual time frames most frequently used for the compress application. The utilization of a thermal compress is recommended for 15 to 20 minutes at a time for 3 to 4 times daily, at least for the first 48 to 72 hours after that extravasation occurs. The actual frequency and duration may vary based on the extent of the extravasation and the agent involved in that extravasation. The intent of the warm compress is to help disperse the agent and reduce the localized accumulation of the agent, whereas the cold compress, it actually helps prevent the dispersion or the spread of the agent while allowing the antidote to help neutralize that agent. Warm compresses are recommended for extravasations involving the vinca alkaloids, etoposide, oxaliplatin, and the taxanes - paclitaxel and docetaxel - only when coadministering the antidote hyaluronidase. The use of a cold compress is actually recommended for extravasations involving the anthracyclines, antimetabolites, alkylating agents, and taxanes when coadministration of the antidote hyaluronidase does not occur. Brittany Harvey: Understood. Those specific and actionable recommendations are really key for clinical practice. So then, following those recommendations, how does the guideline address escalation of care and surgical referral for patients with central line extravasation? Dr. Tanya Thomas: So this topic actually had a lot of discussion. And while there is not enough evidence to make strong recommendations, the expert panel recognized that surgical referrals should be considered in certain scenarios. Dr. Aparna Jotwani: We discussed that certain scenarios would include high-risk populations, such as patients that are receiving DNA-binding vesicants, those with high-volume estimated extravasation, and those with CTCAE grade 2, which would be erythema associated with symptoms such as edema, pain, induration, and phlebitis, or grade 3, which would be symptoms of ulceration or necrosis or concern for severe tissue damage, or grade 4, where you would have a life-threatening consequence extravasation, may have a greater likelihood of benefiting from surgical referral and/or escalation of care as deemed appropriate. Brittany Harvey: Great. And yes, it's really important to provide all of these recommendations that you've both just gone through, even when we're faced with very low evidence. So then, Dr. Thomas, in your view, what is the importance of this guideline, and how will it impact clinical practice? Dr. Tanya Thomas: So when extravasations occur in the clinical setting, members of the interdisciplinary team can be faced with barriers related to where to look for the information, how to find all the relevant information in one concise place, how to provide education to the patient about how to care for the site of extravasation in the home setting, and also when to escalate to specialized teams. This can actually cause some added stress and anxiety, and in certain circumstances, may lead to delays in efficient management. This guideline provides the resource clinicians have been looking for. It includes comprehensive recommendations for antineoplastic extravasations in one guideline while also providing a one-page algorithm with the key information regarding the management of the extravasations. This allows all levels of providers to have evidence-based recommendations regarding initial management of the extravasation, for instance, how to manage the infusion, key site assessment reminders, available antidotes, and the use of thermal compress; the required documentation, recommended follow-up scheduling, in addition to key aspects of the patient education. This type of guidance is not found in any other single document regarding antineoplastic extravasation. Having this document readily available at the point of care potentially can reduce time required for providers to search for management recommendations and also provide consistency in patient education and follow-up management scheduling. It reduces uncertainty within interdisciplinary teams and can help inform policy development for clinicians to approach extravasations with confidence. Brittany Harvey: Absolutely. I agree that this is an incredible resource for clinicians with the recommendations, the algorithm that you mentioned, and the supporting evidence that underpins these recommendations to really provide both efficient and effective care for patients. So beyond the impact for clinical practice, Dr. Jotwani, how will these guideline recommendations affect patients receiving antineoplastic treatment for cancer? Dr. Aparna Jotwani: Exactly. In addition to the clinical care team, we want to help and benefit our patients. So, oncology patients that experience extravasations are at risk for, aside of the side effects of tissue necrosis and infection, they also are at risk for delay of cancer treatment. In making these guidelines, we kept in mind the cost and the efforts for patients, additional visits that they could incur, additional time and supplies for care of the extravasation, as well as cost. Our guideline aims to provide an evidence-based approach to the care of oncology patients receiving antineoplastic intravenous therapy. While there are gaps in the data due to the nature of these events, based on careful literature review, these guidelines serve as a basis for quality, standardized oncology care during extravasation. Personally, I hope our graphics especially can be used across the systems to guide clinical care. Brittany Harvey: Definitely. We hope that these recommendations improve treatment and treatment outcomes for all patients receiving antineoplastic treatment for cancer. So then you've also just mentioned some gaps in the literature. So Dr. Thomas, I'd like to turn to you to wrap us up and ask, what are the outstanding questions for the management of antineoplastic extravasation? Dr. Tanya Thomas: Yes, that's a good question. Two of the main outstanding questions are related to the management of extravasations involving the novel agents and extravasations involving multi-agent regimens. The current literature regarding how to effectively manage the multi-agent regimens, for instance, there is no clear guidance for managing the extravasation for someone who is receiving a regimen that involves simultaneous administration of, let's say, a vinca alkaloid and an anthracycline. One of those agents requires a warm compress while the other requires a cold compress, and there are different antidotes for those two agents. Additionally, there has not been a lot of published information on the impact of extravasation of those novel agents like the antibody-drug conjugates. With the pace of the drug development, a subgroup of the guideline panelists actually are exploring case reports specific to novel agents to help inform some future work. Brittany Harvey: Yes, we'll look forward to learning more about how to address these ongoing issues and potentially impact guideline recommendations in the future as well. So I want to thank you both so much for your work to develop this incredibly important guideline, and thank you for your time today, Dr. Thomas and Dr. Jotwani. Dr. Aparna Jotwani: Thank you for the opportunity. Dr. Tanya Thomas: Yes, thank you. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/supportive-care-guidelines . I also encourage you to check out the companion episode on this guideline on the ONS podcast, available on Amazon Music, Apple Podcasts , Spotify , and YouTube Music . And finally, you can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store . If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

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Postmastectomy Radiation Therapy: ASTRO-ASCO-SSO Guideline 15:38

11 weeks yang lalu15:38

15:38

Dr. Kathleen Horst, Dr. Rachel Jimenez, and Dr. Yara Abdou discuss the updated guideline from ASTRO, ASCO, and SSO on postmastectomy radiation therapy. They share new and updated recommendations on topics including PMRT after upfront surgery, PMRT after neoadjuvant systemic therapy, dose and fractionation schedules, and delivery techniques. They comment on the importance of a multidisciplinary approach and providing personalized care based on individual patient characteristics. Finally, they review ongoing research that may impact these evidence-based guidelines in the future. Read the full guideline, " Postmastectomy Radiation Therapy: An ASTRO-ASCO-SSO Clinical Practice Guideline " at www.asco.org/breast-cancer-guidelines " TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/breast-cancer-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology , https://ascopubs.org/doi/10.1200/JCO-25-01747 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts . My name is Brittany Harvey, and today I am interviewing Dr. Kathleen Horst, expert panel chair from Stanford University; Dr. Rachel Jimenez, expert panel vice chair from Massachusetts General Hospital; and Dr. Yara Abdou, ASCO representative from the University of North Carolina, authors on "Postmastectomy Radiation Therapy: An American Society for Radiation Oncology, American Society of Clinical Oncology, and Society of Surgical Oncology Clinical Practice Guideline." Thank you for being here today, Dr. Horst, Dr. Jimenez, and Dr. Abdou. Dr. Kathleen Horst: Thank you for having us. Brittany Harvey: And then just before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Horst, Dr. Jimenez, and Dr. Abdou who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology , which is linked in the show notes. Then to dive into the content that we are here today to talk about, Dr. Horst, could you start us off by describing what prompted the update for this joint guideline between ASTRO, ASCO, and SSO, and what is the scope of this 2025 guideline on postmastectomy radiation therapy? Dr. Kathleen Horst: Thank you. This joint guideline was last updated in 2016. Over the past decade, the treatment of breast cancer has evolved substantially. Newer systemic therapy regimens have increasingly personalized treatment based on tumor biology, and local therapy management has explored both the de-escalation of axillary surgery and more abbreviated courses of radiation therapy. Given these advances, it was important to revisit the role of postmastectomy radiotherapy in this modern era of breast cancer therapy. This updated guideline addresses four key questions, including postmastectomy radiation therapy after upfront surgery as well as after neoadjuvant systemic therapy. It also reviews the evolving role of various dose and fractionation schedules and optimal treatment techniques and dose constraints. Brittany Harvey: Excellent. I appreciate that background, Dr. Horst. So then, next, Dr. Jimenez, I would like to review the recommendations of this guideline across those four key questions that Dr. Horst just mentioned. So first, what does the panel recommend for PMRT for patients who received initial treatment with mastectomy? Dr. Rachel Jimenez: The panel provided pretty strong consensus that patients with positive lymph nodes or patients with large tumors involving the skin or the chest wall should receive postmastectomy radiation. However, the panel also recognized that the omission of postmastectomy radiation may be appropriate for select patients who have positive lymph nodes and have an axillary lymph node dissection if they have a low nodal burden and other favorable clinical or pathologic features. For patients without lymph node involvement at the time of surgery and no involvement of the skin or chest wall, postmastectomy radiation was not advised by the panel. Brittany Harvey: Understood. It is helpful to understand those recommendations for that patient population. Following that, Dr. Abdou, what are the key recommendations for PMRT for patients who received neoadjuvant systemic therapy before mastectomy? Dr. Yara Abdou: When we think about PMRT after neoadjuvant treatment, the key point is that the initial stage of presentation still matters a lot. So for example, if a patient comes in with more advanced disease, say a large primary tumor, like a clinical T4, or more extensive nodal disease, like an N2 or N3 disease, those patients should get PMRT, no matter how well they respond to neoadjuvant therapy, because we know it reduces the risk of recurrence and that has been shown pretty consistently. On the other hand, if there are still positive lymph nodes after neoadjuvant treatment, basically residual nodal disease, PMRT is also strongly recommended because the risk of local-regional recurrence is much higher in that setting. The gray area is the group of patients who start with a lower burden of nodal disease, such as N1 disease, but then become node negative at surgery. For those patients, we tend to individualize the decision. So if the patient is young or has triple-negative disease, or if there is a lot of residual disease in the breast even though the nodes are cleared, then radiation is probably helpful. But if everything has melted away with pCR in both the breast and the nodes, then it may be safe to omit PMRT in those patients. For patients with smaller tumors and no nodal involvement to begin with, like a clinical T1-T2 N0, if they are still node negative after neoadjuvant treatment, then PMRT is generally not recommended because their baseline recurrence risk is low. And finally, if the margins are positive and cannot be re-excised, then PMRT is recommended after neoadjuvant therapy. Brittany Harvey: Yes, those distinctions are important for appropriate patient selection. So then, Dr. Horst, we have just reviewed the indications for PMRT, but for those patients who receive PMRT, what are the appropriate treatment volumes and dose fractionation regimens? Dr. Kathleen Horst: The guideline addresses coverage of the chest wall and regional nodes with a specific discussion of the data regarding internal mammary nodal irradiation, which has been an area of controversy over many years. The guideline also reviews the data exploring moderate hypofractionation, or shorter courses of radiation therapy. The task force recommends utilizing moderate hypofractionation for the majority of women requiring postmastectomy radiation, which is likely to have a large impact on clinical practice. This recommendation is based on the evolving data demonstrating that a 3-week course of radiotherapy after mastectomy provides similar oncologic outcomes and minimal toxicity for most patients compared to the standard 5-week treatment course. Brittany Harvey: Thank you for reviewing that set of recommendations as well. So then, Dr. Jimenez, to wrap us up on the key questions here, what delivery techniques are recommended for treating patients who receive PMRT? Dr. Rachel Jimenez: So this portion of the guideline is likely to be most helpful for radiation oncologists because it represents the most technical part of the guideline, but we do believe that it offers some important guidance that has, to this point, been lacking in the postmastectomy radiation setting. So first, the panel recommends that all patients should undergo 3-dimensional radiation planning using CAT scan based imaging, and this includes contouring. So contouring refers to the explicit identification, using a drawing interface on the CAT scan imaging, by the radiation oncologist to identify the areas that are targeted to receive radiation, as well as all of the nearby normal tissues that could receive unintended radiation exposure. And we also provide radiation oncologists in the guideline with suggestions about how much dose each target tissue should receive and what the dose limits should be for normal tissues. Additionally, we make some recommendations regarding the manner in which radiation is delivered. So for example, we advise that when conventional radiation methods are not sufficient for covering the areas of the body that are still at risk for cancer, or where too high of a dose of radiation would be anticipated to a normal part of the body, that providers employ a technique called intensity modulated radiation therapy, or IMRT. And if IMRT is going to be used, we also advise regular 3-dimensional imaging assessments of the patient's body relative to the treatment machine to ensure treatment fidelity. When the treatments are delivered, we further advise using a deep inspiration breath-hold technique, which lowers the exposure to the heart and to the lungs when there is concern for cardiopulmonary radiation exposure, and again, that image guidance be used along with real-time monitoring of the patient's anatomy when those techniques are employed. And then finally, we advise that patients receiving postmastectomy radiation utilize a bolus, or a synthetic substance placed on the patient's skin to enhance radiation dose to the superficial tissue, only when there is involvement of the skin with cancer or other high-risk features of the cancer, but not for every patient who receives postmastectomy radiation. Brittany Harvey: Understood. And then, yes, you just mentioned that section of the guideline is probably most helpful for radiation oncologists, but I think you can all comment on this next question. What should all clinicians, including radiation oncologists, surgical oncologists, medical oncologists, and other oncologic professionals, know as they implement all of these updated recommendations? Dr. Rachel Jimenez: So I think one of the things that is most important when we consider postmastectomy radiation and making recommendations is that this is a multidisciplinary panel and that we would expect and encourage our colleagues, as they interpret the guidelines, to employ a multidisciplinary approach when they are discussing each individual patient with their surgical and medical oncology colleagues, that there is no one size fits all. So these guidelines are intended to provide some general guidance around the most appropriate techniques and approaches and recommendations for the utilization of postmastectomy radiation, but that we recognize that all of these recommendations should be individualized for patients and also represent somewhat of a moving target as additional studies, both in the surgical and radiation oncology realm as well as in the systemic therapy realm, enter our milieu, we have to adjust those recommendations accordingly. Dr. Kathleen Horst: Yeah, I would agree, and I wanted to comment as a radiation oncologist, we recognize that local-regional considerations are intertwined with systemic therapy considerations. So as the data evolve, it is critical to have these ongoing updates in a cross-disciplinary manner to ensure optimal care for our patients. And as Dr. Jimenez mentioned, these multidisciplinary discussions are critical for all of us to continue to learn and understand the evolving recommendations across disciplines but also to individualize them according to individual patients. Dr. Yara Abdou: I could not agree more. I think from a medical oncology perspective, systemic therapy has gotten much better with adjuvant CDK4/6 inhibitors, T-DM1, capecitabine, and immune therapy. So these are all newer adjuvant therapies, so the baseline recurrence risks are lower than what they were in the trials that established PMRT. So the absolute benefit of radiation varies more now, so smaller for favorable biology but still relevant in aggressive subtypes or with residual disease. So it is definitely not a one-size-fits-all. Brittany Harvey: Yes, I think it is important that you have all highlighted that multidisciplinary approach and having individualized, patient-centric care. So then, expanding on that just a little bit, Dr. Abdou, how will these guideline recommendations affect patients with breast cancer? Dr. Yara Abdou: So basically, reiterating what we just talked about, these guidelines really move us towards personalized care. So for patients at higher risk, so those with larger tumors, multiple positive nodes, or residual nodal disease after neoadjuvant therapy, PMRT remains essential, consistently lowering local-regional recurrence and improving survival. But for patients at intermediate or lower risk, the recommendations support a more selective approach. So instead of a blanket rule, we now integrate tumor biology, response to systemic therapy, and individual patient factors to decide when PMRT adds meaningful benefit. So the impact for patients is really important because those at high risk continue to get the survival advantage of radiation while others can be spared the unnecessary treatment and side effects. So in short, we are aligning PMRT with modern systemic therapy and biology, making sure each patient receives the right treatment for their situation. Brittany Harvey: Absolutely. Individualizing treatment to every patient will make sure that everyone can achieve the best outcomes as possible. So then, Dr. Jimenez, to wrap us up, I believe Dr. Horst mentioned earlier that data continues to evolve in this field. So in your opinion, what are the outstanding questions regarding the use of PMRT and what are you looking to for the future of research in this space? Dr. Rachel Jimenez: So there are a number of randomized phase III clinical trials that are either in active accrual or that have reported but not yet published that are exploring further de-escalation of postmastectomy radiation and of axillary surgery. And so we do not yet have sufficient data to understand how those two pieces of information integrate with each other. So for example, if you have a patient who has a positive lymph node at the time of diagnosis and forgoes axillary surgery aside from a sentinel lymph node biopsy, we do not yet know that we can also safely forgo radiation entirely in that setting. So we expect that future studies are going to address these questions and understand when it is appropriate to simultaneously de-escalate surgery and radiation. Additionally, there is a number of trials that are looking at ways in which radiation could be omitted or shortened. So there is the RT CHARM trial, which has reported but not yet published, looking at a shorter course of radiation. And so we do make recommendations around that shorter course of radiation in this guideline, but we anticipate that the additional data from the RT CHARM study will provide further evidence in support of that. Additionally, there is a study called the TAILOR RT trial, which looks at forgoing postmastectomy radiation in patients who, to Dr. Abdou's point, have a favorable tumor biology and a low 21-gene recurrence score. And so we are going to anticipate the results from that study to help guide who can selectively forgo postmastectomy radiation when they fall into that favorable risk category. So there are a number of questions that I think will help flesh out this guideline. And as they publish, we will likely publish a focused update on that information to help provide context for our colleagues in the field and clarify some of these recommendations to suit the latest data. Brittany Harvey: Absolutely. We will look forward to those de-escalation trials and ongoing research in the field to build on the evidence and look for future updates to this guideline. So I want to thank you for your work to update these guidelines, and thank you for your time today, Dr. Horst, Dr. Jimenez, and Dr. Abdou. Dr. Rachel Jimenez: Thank you. Dr. Yara Abdou: Thank you. Dr. Kathleen Horst: Thank you. Brittany Harvey: And then finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/breast-cancer-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store . If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

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Geriatric Assessment Global Guideline 16:19

13 weeks yang lalu16:19

16:19

Dr. Cris Bergerot and Dr. Enrique Soto join the podcast to discuss the new global guideline on geriatric assessment. This guideline provides evidence-based, resource-stratified recommendations across the basic, limited, and enhanced settings. Dr. Bergerot and Dr. Soto discuss who should receive a geriatric assessment, the role of geriatric assessment, which elements of geriatric assessment can help predict adverse outcomes, and how a geriatric assessment is used to guide care and make treatment decisions. They comment on the importance of this guideline worldwide, and the impact of this guideline for a wide range of clinicians, patients, researchers, policymakers, and health administrators. Read the full guideline, "Geriatric Assessment: ASCO Global Guideline" at www.asco.org/global-guidelines ." TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/global-guidelines . Read the full text of the guideline, view clinical tools and resources, and review authors' disclosures of potential conflicts of interest in the JCO Global Oncology , https://ascopubs.org/doi/10.1200/GO-25-00276 Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts . My name is Brittany Harvey, and today I'm interviewing Dr. Cris Bergerot from OncoClínicas & Co and Dr. Enrique Soto from the University of Colorado, co-chairs on "Geriatric Assessment: ASCO Global Guideline". Thank you for being here today, Dr. Bergerot and Dr. Soto. Dr. Cris Bergerot: Thank you. Dr. Enrique Soto: Thanks for the invitation, Brittany. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Bergerot and Dr. Soto who have joined us here today, are available online with the publication of the guideline in JCO Global Oncology , which is linked in the show notes. So then to jump into the guideline here, Dr. Soto, could you start by providing an overview of the scope and the purpose of this global guideline on geriatric assessment? Dr. Enrique Soto: Of course, Brittany. So, this guideline comes from a request from the global oncology community and from the geriatric oncology community, who is very interested in making sure that geriatric oncology recommendations that are used in the United States can be adopted and used globally. So, this was a very highly rated topic when we had our call for proposals for guidelines, and that's why we decided to do this. The idea of this guideline is to provide resource-stratified recommendations for the use of geriatric assessments and interventions in older adults with cancer across different settings, right? And that these guidelines can be applied by clinicians working in low- and middle-income countries, but also, in a way, by clinicians working in community settings where the availability of resources may be limited. And the idea of these recommendations is to help clinicians evaluate older people with cancer better and also understand which interventions can be implemented with the resources they have and which interventions have a bigger bang for the buck, so to speak. And as all evidence-based, stratified guidelines that ASCO conducts, we stratified resources as basic, limited, or enhanced. And that means resources that go from those that provide the greatest benefits for patients in terms of outcomes to those that are evidence-based but provide additional additive benefits. And those resource-stratified recommendations can be found in the ASCO website as to how these guidelines are developed, and that's pretty standard for most resource-stratified guidelines. Brittany Harvey: Great. I appreciate that background and the impetus for this guideline, and thank you for providing that resource-stratified framework of basic, limited, and enhanced. I think that helps provide context for the guideline recommendations here. So then, Dr. Bergerot, I'd like to next review the key recommendations of this guideline across the four clinical questions that the guideline addresses. So, across those settings, the basic, limited, and enhanced settings, what is the role of geriatric assessment in older adults with cancer to inform specific interventions? Dr. Cris Bergerot: I think this is one of the most important points, so let's break it down. First off, who should actually receive the geriatric assessment? And the recommendation is clear. All patients aged 65 and older who are being considered for systemic cancer therapy should undergo a geriatric assessment. Now, depending on the available resources, for example, in basic setting, a quick screening may be enough, but in enhanced setting, a comprehensive geriatric assessment is encouraged. And for our next question, in which elements of the geriatric assessment can help predict poor outcomes, the core domains to focus on include things like physical function, comorbidities, polypharmacy, cognition, nutrition, social support, and psychological health. And there are also validate tools like the G8, the CGA, and the CARG that can be used depending on the setting and resources available. Now, talking about how we actually use the geriatric assessment to guide care, the assessment results can guide interventions to reduce treatment-related toxicities and maintain the patient functions. So, even in basic settings, the result can help guide those adjustments or identify the need for supportive care. And in more resource settings, we can implement more tailored intervention based on those findings. And finally, for our fourth question: How can geriatric assessment help guide treatment decisions? So, GA can influence decisions about how aggressive treatment should be, help clarify goals of care, and determine whether a curative or palliative approach makes the most sense. And again, even in settings with limited resources, a simplified GA can still provide meaningful guidance. Brittany Harvey: Great. Thank you, Dr. Bergerot, for that high-level overview of the recommendations of this guideline. So then, following that, Dr. Soto, which geriatric assessment tools and elements should clinicians use to predict adverse outcomes for older patients receiving systemic therapy across the basic, limited, and enhanced settings? Dr. Enrique Soto: Yeah, so that is an excellent question because it's something that people want to know, right? When people start developing a geriatric oncology clinic, one of the first things they want to know is which tools should I use. And we hope that this guideline will provide some clarity regarding this. So, our overarching recommendation is that every patient, regardless of the level of resources, should receive some sort of geriatric assessment. And that geriatric assessment can go from a simple screening tool, such as the G8 tool, which is available online and very easy to do, and that can be done in basic settings, to a more sophisticated geriatric assessment. The important thing, and what we emphasize in the guideline, is that regardless of the tool you use, it should include those high-priority domains that are associated with outcomes in older adults with cancer. And those include an assessment of physical function, of cognition, emotional health, comorbidities, polypharmacy, nutrition, and social support. In addition to that, an important thing that the guideline does is endorse the recommendation from our parent guideline, the guideline from high-income settings, the practical geriatric assessment , which is a tool that was actually developed by the ASCO Geriatric Oncology Group, which is a self-administered tool that people can use to evaluate their patients in a prompt and fast manner. And what we actually did for this guideline is include the validation of the various tools included in the practical geriatric assessment in the five most widely spoken languages in the world, including Hindi, Chinese, Spanish, and French, and Portuguese. And so, most of these tools are validated in these languages. So, we believe that the practical geriatric assessment is a tool that can be utilized across settings and that doesn't require a lot of resources. I think an important future step is making sure that we get the practical geriatric assessment translated into various languages, and we're working with the ASCO team in getting that done. Brittany Harvey: That's an excellent point. And yes, we'll hope to have the practical geriatric assessment translated into more languages. And that tool is available linked in the guideline itself, and we'll also provide a link for listeners in the show notes of this episode ( Practical Geriatric Assessment ). So then, following that, Dr. Bergerot, in resource-constrained settings, what general life expectancy data should clinicians use to estimate mortality and inform treatment decision-making? Dr. Cris Bergerot: So, in basic and limited resource environments, you might not have access to every tool or specialist, but you can still make informed and thoughtful decisions. So, what the guideline recommends is to start with population-level life expectancy tables. These are available through the WHO Global Health Observatory, and they offer useful starting points. And if available, clinicians should also look for country-specific or regional survival data. That kind of local information can be even more relevant to your patient population. The clinical judgment is also key here, and it becomes even more powerful when it's guided by the patient's geriatric assessment results. And when possible, use age- and comorbidity-adjusted models, like the Lee index or tools from the ePrognosis. This can help refine estimates of mortality risk and also inform how aggressive treatment should be. Brittany Harvey: Absolutely. I appreciate you providing those specifics as well. So then, following that, Dr. Bergerot mentioned this a little bit earlier, but Dr. Soto, how should geriatric assessment be used to guide management of older patients with cancer across the basic, limited, and enhanced settings? Dr. Enrique Soto: Yeah, and again, that's another important focus, right? Because if we assess things and then don't do anything about them, then why even assess them, right? And in many settings, people say, "Well, I don't have the tools to provide the interventions that these patients actually need." And a very significant part of building this guideline was coming up with a resource-stratified and evidence-based way in which to prioritize which interventions provide most benefits for older adults with cancer. And so, for each level and each domain, we have a series of interventions that have been stratified according to importance and evidence base, and that is actually one of the coolest features of the guideline. We included a table, and then we have for each of the domains, including falls, functional status, weight loss, et cetera, what are the interventions that oncologists can do in their clinical visit without needing a lot of resources, including providing some specific information, giving some recommendations to patients, to more high-level things that can be done when the healthcare system allows it, such as working with a nutritionist, providing supplements, testing for particular cognitive impairments, et cetera. So, I encourage people to take a look at that table. It was really a lot of work putting that table together, and that table has specific recommendations for each setting, and I think people will find it very useful. Brittany Harvey: Absolutely. That table certainly contains a lot of information that's very helpful for clinicians. I think it's important to call out those tailored interventions to improve care and quality of life for every patient. So then, we've just reviewed all of the recommendations in this guideline. So, I'd like to ask you, Dr. Bergerot, in your opinion, what should clinicians know as they implement these recommendations across resource levels? Dr. Cris Bergerot: I would say that clinicians should remember that even a brief geriatric assessment can make a meaningful difference. You don't need a full suite of tools to improve quality of care, but clinicians should tailor all the tools that are available in their local context and always keeping in mind the core geriatric domains that we have mentioned in the very beginning of our podcast. And let's be clear, the goal of the assessment isn't just to gather data, as Enrique mentioned; it's to use this information to guide treatment decision and also to improve outcomes. And whenever possible, clinicians should engage interdisciplinary teams that might include nurse, psychologist, social workers, community health workers, or anyone who can help address the patient's broader needs. And flexibility really matters. So, especially in settings with limited access to specialists or diagnostics, we should prioritize what is feasible and what will truly help our patients during their journey. And above all, we should keep this in mind that equity in care delivery is essential. Just because resources are limited doesn't mean we can't deliver age-sensitive and even patient-centered care. Brittany Harvey: Definitely. That multidisciplinary care that you mentioned is key, and also thinking about what is feasible across every resource level to provide optimal care for every single patient. So then, to expand on that just a little bit and to wrap us up, Dr. Soto, what is the impact of this guideline for older adults with cancer globally? Dr. Enrique Soto: Well, what we hope this guideline will lead to is to a boom in geriatric oncology worldwide, right? That is our final goal. And what we want is for clinicians interested in starting a geriatric oncology program or setting up a geriatric oncology clinic to use these guidelines in order to justify the interventions that they're going to do, to pick the important partners they need for their multidisciplinary team, to choose the tools that they're going to implement. And then, with that, to present this to leaders in their hospitals, leaders in their healthcare system so that they can start these clinics that will ultimately lead to better outcomes for older adults with cancer. So, I encourage people to view this as high-quality, evidence-based recommendations that are done by a group of experts and with a thorough review of the literature and also based on our parent guidelines. The fact that these guidelines are resource-stratified does not by any mean signify that they're of less quality or that the recommendations that are included in those are not proven to improve outcomes, cancer-specific and also general outcomes, in older adults with cancer. Another thing that I think these guidelines could do in the future is motivate researchers in low- and middle-income countries to fill in the gaps that we have identified in these guidelines. We've made it very clear across the guidelines where evidence is lacking. And I think that this should prompt researchers across the globe to start trying to fill in these gaps with high-quality research. And finally, I also think that this is a call for policymakers, health administrators, and people interested in public health to start scaling up resources so that places with basic resources can eventually become places with more sophisticated resources. And I think this does not only apply to low- and middle-income countries, but also to community oncologists in the US who may be facing resource constraints. And I think that these guidelines can help them stratify and understand what things should be implemented first and how to scale up. So yeah, that's the dream that with this guideline, more people will start implementing geriatric oncology around the globe and that ASCO will continue to be a leader in setting the stage for what should be done in geriatric oncology and for improving care to older adults with cancer, regardless of where they live. Brittany Harvey: Absolutely. This guideline is wide-reaching and has important impacts worldwide. So, I want to thank you both so much for the huge amount of work you took to develop this evidence-based guideline, and thank you for joining me on the podcast today, Dr. Bergerot and Dr. Soto. Dr. Cris Bergerot: Thank you so much. Dr. Enrique Soto: Thank you for the invitation. It was a pleasure. Brittany Harvey: And finally, thank you to our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/global-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

1
Oncology Medical Homes: ASCO-COA Standards Update 16:11

19 weeks yang lalu16:11

16:11

Ms. Kim Woofter and Dr. John Cox discuss the latest updates to the evidence-based standards on oncology medical homes developed by ASCO and COA. These standards serve as the basis for the ASCO Certified program. They share the new and revised standards around topics including the culture of safety and just culture in oncology practice, geriatric assessment and geriatric assessment-guided management, and multidisciplinary team management. They expand on the importance of these standards for clinicians and oncology practices to ensure every patient receives optimal care. Read the complete standards, "Oncology Medical Homes: ASCO-Community Oncology Alliance Standards Update" at www.asco.org/standards . TRANSCRIPT These standards, clinical tools, and resources are available at www.asco.org/standards . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the JCO Oncology Practice , https://ascopubs.org/doi/10.1200/OP-25-00498 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts . My name is Brittany Harvey, and today I'm interviewing Ms. Kim Woofter, a registered nurse in practice leadership and administration from AC3 Inc in South Bend, Indiana, and Dr. John Cox, a medical oncologist and adjunct faculty member from UT Southwestern Medical Center in Dallas, Texas, co-chairs on "Oncology Medical Homes, American Society of Clinical Oncology – Community Oncology Alliance Standards." Thank you for being here today, Ms. Woofter and Dr. Cox. Dr. John Cox: You bet. Ms. Kim Woofter: Thank you. Brittany Harvey: And then before we discuss these standards, I'd just like to note that ASCO takes great care in the development of its standards and ensuring that the ASCO Conflict of Interest Policy is followed for each guidance product. The disclosures of potential conflicts of interest for the expert panel, including Dr. Cox and Ms. Woofter, who have joined us here today, are available online with the publication of the standards in JCO Oncology Practice , which is linked in the show notes. So then, to dive into what we're here today to talk about, Dr. Cox, could you start us off by explaining what prompted an update to these ASCO-COA standards and what the scope of this update is? Dr. John Cox: Well, the ASCO-COA standards relative to defining and outlining Oncology Medical Home were initially published four or five years ago. At the time, we planned a regular update of the standards. So, in essence, this is a planned update. The whole program is built on the idea of continuous improvement. So, this update and future updates are prompted and defined by our literature, our science, the science of care delivery, and new developments and insights gained from studies and evaluations of care delivery methods, and informed by the practice. These standards are in place to underpin a program of care delivery by ASCO, the ASCO Certified, and as practices engage in this program, we are learning from them. The whole idea is to enlarge and improve how patients are cared for in practice. Brittany Harvey: Absolutely. It's great to have this iterative process to continue to review the evidence and update these standards that form the basis for ASCO Certified. So then, following that background, Ms. Woofter, I'd like to review the key points of the revised standards for our listeners. First, how do the revised standards address the culture of safety and just culture in oncology practice? Ms. Kim Woofter: I think safety is of utmost importance to all of us. So let me say that first and foremost. And what we know in oncology is our QOPI standards already address safety in the infusion suite process. So, safe delivery of chemotherapy agents and antineoplastics. It also talked about near misses and medication errors - absolutely essential, for sure. But what we need to do is look at a more systemic approach to safety because we know is processes throughout an organization they'll often cause you trouble. To do that, we know you need what we call a just culture, which is a very common term in today's workplace. But what it really means is it's a culture of open reporting of any potential for error, any potential for malfunction, and it can be in any place in the organization. So, what we are doing in our new standard is to say, look at your entire processes throughout the organization, and approach that in an open-minded way so that people don't feel scared to report things, and it's a really positive approach to intervening early and making sure that errors don't occur anywhere in the workplace. Brittany Harvey: Taking that systemic approach to look at overarching processes seems really key to ensuring safety in oncology practices. So then, the next new section, Dr. Cox, what are the new OMH standards surrounding geriatric assessment and geriatric assessment–guided management? Dr. John Cox: This is a challenging update for our standards. As many folks in practice recognize, there is a deep literature on recognizing the geriatric population in oncology. Geriatric - those in my age group over age 60, 65 - make up the majority of cancer patients in this country. And yet, there are many aspects that should be taken into account as you address treatment decisions in this population. ASCO's recognized this. There has been a guideline previously on geriatric assessment. It's been updated, and we really felt it's time that it be incorporated in any iteration of what oncology care delivery means, so, within the oncology medical home standards. In short, what the standard outlines is that practices that are using these standards, that are using this benchmark, should have a geriatric assessment for patients within the practice care and use that information to guide management. Now, the standard allows wide exploration of how practices meet this standard, but it really puts on the table that if an oncology practice in the United States, or anywhere in the world really, is adhering to a good practice, that they're going to include and recognize these assessments in practice. Ms. Kim Woofter: I would like to add that this is a highly discussed and reviewed standard. Many of our community practices were concerned that they would have the time and manpower to perform this assessment. We all know it reduces toxicities if done appropriately at treatment planning, and so the outcomes are better. And we really left it to the practices to define how they're going to implement it, understanding that it will evolve to every single patient, but maybe day one, it was a step approach to be able to implement. So, I was really proud of the team that - the expert panel - that said, okay, let's step into this, but we do think it's essential. Brittany Harvey: Absolutely. It's important to recognize that practices may have limited resources and time, and implementing it in the way that makes sense for them allows this to be a standard that can be used in practice. And it's great to have this geriatric assessment guideline integrated into these standards to improve care delivery. And we can provide a link to that guideline in the show notes of this episode as well ( Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update ). So then, following that section of the standards, Ms. Woofter, how do the updated standards now address multidisciplinary team management? Ms. Kim Woofter: Well, we address multidisciplinary team management in a more comprehensive way in the updated standard. We always thought that that was a critical piece when doing treatment planning, and we kind of highlighted it in a bigger way, understanding that not everybody has the same resources available at the time of treatment planning. And again, this was a much-discussed standard, in that that multidisciplinary team approach doesn't necessarily have to be in a tumor board or a prospective analysis of every case. It is actually a conversation between specialists, between the surgeon and pathologist and the medical oncologist. And we are saying, do what works for you, but we know that that team approach, every specialty coming to the table at time of treatment planning, truly provides better outcomes for our patients. And so we kind of reiterated that, understanding that again, it doesn't have to be a formal tumor board, but it has to be a dialogue between specialties. And we highlighted that again in the new standard. Brittany Harvey: Open communication of all team members is really critical to providing optimal care. Dr. Cox, I'd like to ask you, in your view, how will these updated standards impact both clinicians and oncology practices? Dr. John Cox: Well, our whole goal with discussing a comprehensive care model for oncology practice is to have a benchmark, to have an iteration of what good oncology care delivery looks like. So, our hope is that practices, all practices, whether you're participating formally in ASCO Certified, the marquee quality program for ASCO, or if you are simply running a practice or a team within an academic environment or institutional environment, these standards are to apply across the board wherever oncology is practiced - that you can look at these standards as a benchmark and compare what you are doing in your practice and where are the gaps. So ideally, we drive improved care across the board. You know, one thing I've learned over the last couple of years as ASCO Certified is getting spun up and using and implementing these standards, is practices are remarkably innovative. We've learned a lot by seeing how pilot practices have met the standards, and that's gone into informing how we can improve care delivery for all of our practices and, importantly, for the team members who are delivering this care. The fourth rail of burnout and the like is inefficiency that occurs in practice. And when you know you've got a good, spun-up, effective team, less burnout, less stress for practice. I hope clinicians and oncology practices will use this to help drive improvements in their care and gain insight into how they can approach practice problems in a better way. Kim, you've been leading practices. I have to ask you, your thoughts in leaning into this question. Ms. Kim Woofter: I think very well said, I will say that first. And what I love about this is for practice leaders who are new to our ecosystem, if you will, they need a playbook. It's "Where do I begin?" And Dr. Cox said it very well, no one does everything perfectly day one, but it's a step-by-step self-assessment approach to say, "How do I get to this gold standard?" I really love the standards because they are very comprehensive, everything from treatment planning to end of life. So it's the spectrum of the care we deliver in the oncology setting. So as a leader and an administrator, it is the standard I want all of my departments to understand, adhere to, and engage, and be excited about. We now have a baseline approach, and what's even more important, these standards will evolve as our intelligence evolves, as literature evolves. It's a system that will always grow and change, and that's what we love about it. It's not a one-and-done. So, I'm very proud of the fact that it gives them a road map. Brittany Harvey: Yes, these evidence-based standards provide a critical foundation for practices in ASCO Certified, for those team members you mentioned, and for quality improvement beyond just those individuals and practices as well. So then finally, to wrap us up, Ms. Woofter, what do these revised standards mean for patients receiving cancer treatment? Ms. Kim Woofter: Well, I think that's the most exciting part, is we all do this for our patients and the best outcomes for our patients and the best treatment plans for our patients and their families. And these standards, that is their core, their absolute core. So what it's going to do for a patient is they can say, "Am I at a practice that implements ASCO standards?" And if that is a 'yes', there's a confidence that, "I am in an evidence-based medicine thinking practice, I have a team around me, they will care for me not only at time of treatment planning but at the time of end of life, they will help me be part of that decision-making, and they will give me resources available to me in my community." So, it is a true comprehensive approach. As a patient, I have that comfort, that it is bigger than just a great doctor. It is a great team. As a patient, that would be very important to me and important to my family. That being said, Kim Woofter would love every practice to be ASCO Certified. Understanding that that isn't feasible day one, just to know that the practice is implementing and engaging the standards is the great place to start. Every patient can't go to an ASCO Certified practice day one, but our dream would be that everyone would adhere to those standards, engage those standards, believe them, educate their staff on what they mean, so that patient outcomes and satisfaction will be optimized for everyone. The other piece to this that we all know is if you give evidence-based medicine, cost-effective, efficient care, it's better for the system as a whole. And I'm not saying that insurance is our driver - certainly patient outcomes are our driver - but the whole ecosystem of oncology benefits when you do the right thing. Dr. John Cox: It's hard to add anything to Kim's good statements, but I just highlight that this whole area began with the patient-centered medical home, and every time we've met, patients and how we deliver care to patients is top of mind. I think that reflects our community. It reflects oncology as a whole. I don't know any oncologist or practice that is focused on anything else as the prime goal. Brittany Harvey: That's what I was just going to say. The ultimate goal here is to provide patient-centered care across where every single patient is receiving treatment and at every stage of that treatment. So, I want to thank you both so much for your work to update these standards, to review the evidence, and discuss with the experts on the panel to come up with the solutions that will help drive quality improvement across care delivery. So, thank you for that, and thank you for your time today, Dr. Cox and Ms. Woofter. And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the complete standards, go to www.asco.org/standards . You can also find many of our standards and interactive resources in the free ASCO Guidelines app, which is available on the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

1
Therapy for Stage IV NSCLC With Driver Alterations: ASCO Living Guideline Update 2025.1 Part 2 15:16

19 weeks yang lalu15:16

15:16

Dr. Joshua Reuss joints that podcast to discuss the latest changes to the living guideline on stage IV NSCLC with driver alterations. He discusses the new evidence for NSCLC with EGFR mutations and NRG1 fusions and how this impacts the latest recommendations from the panel. He shares ongoing research that the panel will review in the future for further updates to this living guideline, and puts the updated recommendations into context for clinicians treating patients with stage IV NSCLC. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2025.1" at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology , https://ascopubs.org/doi/10.1200/JCO-25-01061 Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast , one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts . My name is Brittany Harvey, and today I'm interviewing Dr. Joshua Reuss from Georgetown University, co-chair on "Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2025.1." It's great to have you here today, Dr. Reuss. Dr. Joshua Reuss: Thank you. Happy to be here. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Reuss, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology , which is linked in the show notes. So to dive into what we're here today to talk about, Dr. Reuss, this living clinical practice guideline for systemic therapy for patients with stage IV non–small cell lung cancer with driver alterations is updated on an ongoing basis. So what prompted this latest update to the recommendations? Dr. Joshua Reuss: Yes, thank you. It's very important that we have living guidelines that are continuously updated. We obviously don't live in a static environment where things are non-changing, and we really need to apply the most up-to-date and current evidence to treat our patients with the most effective strategies, the most groundbreaking strategies. And so to have guidelines that can be disseminated, particularly these ASCO guidelines, to treating providers is incredibly important. So, with any of these updates, we review ongoing studies, published work, for the quality of evidence to see if it's something that warrants making adjustments to our guidelines or at least incorporating the information so that providers can review it and incorporate this into their own personal decision-making. So in this particular update, we reviewed evidence particularly pertaining to EGFR -mutated non–small cell lung cancer and non–small cell lung cancer harboring an NRG1 fusion. Brittany Harvey: Yes, certainly there's a lot of new evidence in the advanced non–small cell lung cancer field, and so we appreciate the panel's continuous review of this evidence. So then you just mentioned two separate areas where the panel reviewed new evidence. So starting with that first one, what updated evidence did the panel review on first-line treatment options for patients with EGFR alterations, and how did this impact the recommendations? Dr. Joshua Reuss: Yes, so advanced EGFR -mutated non–small cell lung cancer, at least with classical activating alterations - that is our exon 19 deletions and our exon 21 L858R mutations - is something that's really evolved rapidly in the last few years. You know, for many years, we basically, for the frontline treatment setting, were saying, "Okay, we have a targeted therapy, osimertinib. We're going to give that, and we're going to see what effect we can get out of that," with, you know, a median time of duration of treatment response averaging around 18 months, knowing that there are some that that's a lot longer and some that are a lot shorter. But recently, we've seen a lot of data emerging on combination strategies. The guideline has already been updated to incorporate two of these combinations: osimertinib with chemotherapy based off of the FLAURA2 trial, and then the combination of amivantamab with lazertinib based off of the MARIPOSA trial. And that was data on progression-free survival that was published and led to those particular recommendations. Now, more recently, we've seen data come out in smaller, randomized studies for other combinations. And more recently, we reviewed the RAMOSE study. So this was a phase II, open-label, randomized trial for patients with tyrosine kinase inhibitor–naive and really, treatment-naive advanced EGFR -mutated non–small cell lung cancer harboring one of these two classical EGFR alterations, randomized to either osimertinib alone or osimertinib with the combination of ramucirumab, which is an anti-VEGF agent. There's been a lot of data, preclinical and clinical, for the role of VEGF blockade, particularly in EGFR -mutated non–small cell lung cancer, so exploring the combination of this for synergy in the frontline setting really made a lot of sense. So again, this was a phase II trial that randomized patients prospectively to one of these two regimens. The population here is really what we typically see with EGFR -mutated non–small cell lung cancer, predominantly a younger population - median age on this study was 65 - predominantly female - 71% female - and predominantly nonsmokers. Now, what this study showed was that at a median follow-up of 16.6 months, the progression-free survival favored the combination arm with a median progression-free survival of 24.8 months with the combination of osimertinib plus ramucirumab versus 15.6 months for osimertinib alone, for a hazard ratio of benefit of 0.55. The landmark one- and two-year endpoints for progression-free survival also favored the combination arm, and response rates were relatively comparable between groups, with overall adverse events being more frequent in the combination group, specifically high blood pressure, proteinuria, and epistaxis, which are our common adverse events related to VEGF-blocking agents. So, it's good to see data in this space. Now, of note, though, this was a phase II study, so not a phase III level of evidence. In addition, when looking at the population, this was a randomized, multicenter study, but it was a US-only population. There was also some imbalance in the number of visits between arms, so the combination arm was seen more frequently than the arm that got osimertinib alone. Now, the imaging assessments were no different, but obviously this could lead to potential confounding, at least in timing of awareness of potential side effects and and things being brought to the attention of investigators. So very promising data here, but because, you know, of this being a phase II study, this actually led to no changes in the guideline at this time. Brittany Harvey: Understood. Yes, as you mentioned prior, it's important to understand the full body of evidence and to review the trials even when it doesn't impact the recommendations. Dr. Joshua Reuss: And I will say that, you know, there is an ongoing phase III study looking at a very similar combination. It's the phase III ECOG-ACRIN trial of the combination of osimertinib plus bevacizumab versus osimertinib alone in this specific population. So, you know, I think we will see phase III–level data for a combination of VEGF with osimertinib, but again, promising phase II data that did not lead to a change in the recommendation at this time. Brittany Harvey: Absolutely. We'll look forward to that ongoing trial to learn more about combination in this patient population. So then moving to that second patient population that you mentioned earlier where the panel reviewed evidence, what is the updated evidence and recommendation for patients with NRG1 fusions? Dr. Joshua Reuss: Yeah, so this was an exciting update that we made more recently with this unique iteration of the living guidelines. So, NRG1 fusions, this is perhaps a newer kid on the block in terms of driver alterations that has been known to be identified in non–small cell lung cancer among other solid tumors. It is very rare, occurring in less than 1% of solid tumors, but something that we know is a unique oncogenic pathway that can lead to oncogenesis and cancer development, including in non–small cell lung cancer. So up until now, unfortunately, there have not been targeted therapies that target this unique alteration. It's somewhat different than other driver alterations where there's a top-level signaling change in a protein. This is more of a ligand alteration that then alters, that then enables activation of more classical pathways, but again, through upregulation of a unique ligand. So a slightly different pathway but something that we know should be able to be targeted to promote patient survival for those with NRG1 fusions. So the therapy here is a therapy called zenocutuzumab. It's an IgG1 bispecific antibody against HER2 and HER3 . So it prevents the downstream dimerization and signaling that occurs as a result of this NRG1 fusion and upregulation of the NRG1 signal. This was, as you can imagine with a rare alteration, a large phase II registrational study that examined this in advanced solid tumors containing the NRG1 fusion. This is the NRG1 registrational trial. And this study enrolled patients with advanced solid tumors who had progressed on prior therapy. Patients were treated with zenocutuzumab 750 milligrams IV every two weeks. Among 158 response-evaluable solid tumor patients, the response rate was 30%, median duration of response of 11.1 months, and a median progression-free survival of 6.8 months. Now, in those with non–small cell lung cancer, that made up 93 response-evaluable patients, very similar outcomes there: a response rate of 29%, median duration of response of 12.7 months, and a median progression-free survival of 6.8 months. This therapy did appear to be well tolerated. The most common higher-grade emergent side effects - grade 3 or higher - were anemia occurring in 5% and elevated liver numbers occurring in 3%. So this is a subsequent-line study, so this led to the updated recommendation that clinicians may offer zenocutuzumab in the subsequent-line setting for patients with advanced non–small cell lung cancer who harbor NRG1 fusions. So I think this does speak toward the incredible importance of next-generation sequencing and molecular testing for patients, particularly to include testing that looks at the RNA. These large fusions can sometimes be very challenging to detect on DNA sequencing platforms alone, so it's important to, if you have a high level of suspicion for an alteration like this, perhaps some of the mucinous adenocarcinomas where it's been challenging to find a driver alteration, and it's someone who is a never-smoker, really would want to include molecular testing that assesses the RNA level and not just the DNA. Brittany Harvey: Absolutely. It's important to have all the biomarkers available so that clinicians are able to use that to inform their decision-making. So then, given these changes in the guideline, what should clinicians know as they implement this latest living guideline update? And how do these changes impact patients? Dr. Joshua Reuss: Yeah, I think talking in reverse order of what we just discussed here, there is a new guideline update for NRG1 fusions. So I think making sure that that's being evaluated, that clinicians are testing for that and really looking for that result that should be incorporated in in most next-generation large sequencing assays to get that result, but it's very important that that is not overlooked now that we do have a therapy that's available in the subsequent-line setting, though it is important to note that patients with NRG1 fusions, at least the limited data that there is suggests that the efficacy to standard chemoimmunotherapy regimens is overall poor. So physicians unfortunately might be facing this question for second-line therapy in patients with NRG1 fusions sooner rather than later. For the former, for EGFR -altered non–small cell lung cancer and how do we incorporate VEGF-containing regimens into these patients? Our guideline top-level update did not change based off of review of this new study, but it's important for clinicians to know what other combinations may exist. You know, there are phase III studies looking at this combination in the frontline setting. And of course, there is data on other bispecific molecules that incorporate VEGF in the subsequent-line setting, particularly a combination that includes the VEGF/PD-1 bispecific antibody ivonescimab that's being studied in the HARMONi-A trial for patients with EGFR -mutated advanced non–small cell lung cancer, for which we hope to get some more definitive data in the coming months. Brittany Harvey: Definitely. And then you've just mentioned a few ongoing trials where we're looking for evidence to inform future updates. But thinking beyond that, into the future, what is the panel examining for future updates to this living guideline? Dr. Joshua Reuss: It's a very exciting time to be in the world of treating advanced non–small cell lung cancer, particularly patients with driver alterations, because there is so much evolving data that's changing our practice in real time, again highlighting the importance of these living guideline updates. I'd say there's many things that we're excited to see. You know, a lot of the combination regimens in EGFR -mutated non–small cell lung cancer for which there are approvals and current recommendations in our guideline, particularly osimertinib plus chemotherapy and amivantamab plus lazertinib - those are the two approved combination strategies in the front line - we are now seeing the emergence of overall survival data for those combinations. So obviously that is something that's going to be very important for the committee to review and incorporate into guideline updates. There are several new therapies coming down the road for other driver populations. We recently saw an approval for taletrectinib for ROS1 fusion–positive non–small cell lung cancer, so it's going to be important that the committee reviews the data and the publications regarding that therapy. And then there are other novel therapies that we're looking to see updated data on. There are multiple antibody-drug conjugates, which take the potent power of a chemotherapy molecule and attempt to make that targeted with an antibody targeting to a unique feature on the cancer cell. And there are several antibody-drug conjugates that are in development at various levels of promise in this space, particularly in EGFR -mutated non–small cell lung cancer, and I anticipate seeing some emerging data for that coming up in the near future as well. So really, lots to be excited in the space and lots for our committee to review to give guidance on so that these patients can really receive the top-level care wherever they are being treated in the country and throughout the world. Brittany Harvey: Yes, we'll await this new data to continue to provide optimal options for patients with stage IV non–small cell lung cancer with driver alterations. So, Dr. Reuss, I want to thank you so much for your work to rapidly and continuously update and review the evidence for this guideline and thank you for your time today. Dr. Joshua Reuss: Thank you so much. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast . To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available on the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

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Therapy for Stage IV NSCLC Without Driver Alterations: ASCO Living Guideline Update 2025.1 Part 1 11:30

19 weeks yang lalu11:30

11:30

Dr. Lyudmila Bazhenova is back on the podcast to discuss the latest update of the living guideline on therapy for stage IV NSCLC without driver alterations. She shares the studies the Expert Panel reviewed in the first- and second-line settings, including NIPPON, HARMONi-2, and DUBLIN-3. Although these studies do not impact the existing guideline recommendations, Dr. Bazhenova provides context and comments on ongoing trials that will influence the next iteration of the living guideline. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2025.1" at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology , https://ascopubs.org/doi/10.1200/JCO-25-01062 Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts . My name is Brittany Harvey, and today I'm interviewing Dr. Lyudmila Bazhenova from University of California San Diego Moores Cancer Center, co-chair on "Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2025.1." It's great to have you back on the show today, Dr Bazhenova. Dr. Lyudmila Bazhenova: It's my pleasure to be here. Brittany Harvey: And then before we discuss this guideline update, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Bazhenova, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology , which is linked in the show notes. So then to dive into the content here, Dr. Bazhenova, this living clinical practice guideline for systemic therapy for patients with stage IV non–small cell lung cancer without driver alterations is updated on an ongoing continuous basis. So what prompted this latest update to the recommendations? Dr. Lyudmila Bazhenova: Living ASCO guidelines are designed to keep pace with rapidly evolving evidence that impacts treatment of our patients with lung cancer. As a committee, we are tasked with regular review of the published literature and determine if the new data warrants changes to existing recommendations. So in this recently published update, we evaluated new trials related to treatment of patients with metastatic lung cancer without driver alterations. Brittany Harvey: Excellent. Thank you for that explanation of the process. So, you just mentioned that the panel reviewed new trials for this update. So, which particular updated evidence did the panel review on first-line treatment options for patients with good performance status across histology and PD-L1 expression status, and how did this impact the recommendations? Dr. Lyudmila Bazhenova: For the first-line treatment option for patients without driver alterations, two studies met our criteria for review. One was the NIPPON trial from Japan, the second was the HARMONi trial. None of those two trials resulted in change in our guidelines, but I think they are giving us some additional information that would be useful for the way we treat patients with non–small cell lung cancer without driver alterations. For example, if we take those patients, we currently have several treatment options as a first line. One is monotherapy immunotherapy. You can give pembrolizumab as an example, and that was based on the KEYNOTE-024 and KEYNOTE-042 trials. Then we have a platinum doublet plus immunotherapy, and there are several trials that did that pathway. And then we have also an option of giving our patients dual IO immunotherapy combination, such as CheckMate 9LA and POSEIDON. At this point, we do not have any randomized trials comparing those three treatment modalities head-to-head. And the NIPPON trial was interesting to us because it was the first trial to compare CheckMate 9LA regimen, which is again, dual immunotherapy plus chemo, versus KEYNOTE-189 or KEYNOTE-407, which is a chemotherapy plus immunotherapy. And as a result of the study, while chemotherapy plus ipilimumab-nivolumab led to numerically higher overall survival, the difference was not statistically significant. And what is concerning in that trial is that we saw a higher number of treatment-related death occurring in nivolumab and ipilimumab arm compared to the pembrolizumab-chemotherapy arm. As a matter of fact, the trial was terminated early because of the increased risk of death. If you look at the treatment-related death in CheckMate 9LA, the 9LA study reported the treatment-related death to be 2%, and then in the NIPPON trial, the treatment-related death was 7%. Why is that happening? It's really difficult to say. The study was done in Japan. Maybe there is some pharmacogenomic differences between global population and Japan population. But certainly the higher rate of adverse events needs to be taken into account. Another interesting thing about this trial is that it did not show any differences in a subset analysis for patients with squamous histology as well as PD-L1 negative tumor. So while this does not change our current guidelines and CheckMate 9LA treatment still remains an appropriate treatment option, it kind of raises the possibility that this combination could be associated with a higher toxicity. And we do have a randomized US-based trial that is ongoing, and we are hoping that eventually we will be able to answer that question after the trial will be completed. The second trial we reviewed is HARMONi-2. So HARMONi-2 was a randomized, double-blind study which is conducted primarily in China, looking at bispecific PD-L1 and VEGF antibody called ivonescimab. And that took patients who were PD-L1 positive, as defined as more than 1% expression, and patients were randomized to pembrolizumab versus bispecific ivonescimab. And the study was positive. It showed improvement in median progression-free survival of 11 months versus almost 6 months in bispecific versus pembrolizumab. There were, however, higher grade 3 events in the ivonescimab arm. At this point, we are not changing our recommendations because this trial was done in an ex-US population, and we are awaiting a similar trial ongoing in the United States before we change recommendations and decide if ivonescimab needs to be included in our guidelines. Brittany Harvey: This context is very helpful when clinicians think through the data behind these options. And it's important that the panel reviews this evidence, even if it doesn't prompt a change to the recommendations. And we'll await results of those trials that you mentioned to further inform this guideline. So then beyond those studies for first line, what updated evidence did the panel review for second-line and subsequent treatment options for patients with good performance status, and how did this impact the recommendations? Dr. Lyudmila Bazhenova: So for second line, only one trial met the criteria, and that was DUBLIN-3. DUBLIN-3 is a phase 3 single-blind randomized trial comparing docetaxel versus docetaxel plus plinabulin. And the study enrolled patients with second or third line. They have to have had platinum-based chemotherapy and progressed. Plinabulin is an interesting compound. It's a small molecule tubulin binder that prevents polymerization of tubulin and appears to impact dendritic cell maturation and T-cell activation. This study enrolled 559 patients, randomly assigned them to two groups. And one important information about this study is that was a study that was envisioned before immunotherapy became a standard mainstream treatment for first-line therapy. And only 20% of patients had prior PD-1 exposure. So therefore, the results of that study need to be taken into context of this population no longer existing in the United States because we use PD-L1 inhibitors in the first line. And we saw that interesting in the plinabulin arm had lower rates of neutropenia but higher rates of serious adverse events. And at this point, we are not changing our guidelines for mainly two reasons. Number one, low number of patients that received prior treatment with first-line immune checkpoint inhibitors, as well as a modest overall survival benefit of this trial. Brittany Harvey: Understood. I appreciate you describing that study as well and why that evidence didn't prompt a change to those particular recommendations. So then, what should clinicians know as they implement this living guideline, and how does this new evidence impact clinicians and patients? Dr. Lyudmila Bazhenova: At this point, none of the studies that we reviewed resulted in a change in guidelines. We are still waiting for more global results from some of the studies that I highlighted. It shows that there's still a lot of questions we need to be answering in those patients. And I'm hoping that with future clinical trials, we will be able to definitively maybe recommend one treatment over another. But at this point, all the treatments that I mentioned before remain appropriate for patients with stage IV non–small cell lung cancer without driver alterations. Brittany Harvey: Definitely. And then you just mentioned that there's still a lot of outstanding questions in this field. You've mentioned a couple different studies where we're awaiting evidence. Beyond those that you already mentioned, what is the panel examining for future updates to this living guideline? Dr. Lyudmila Bazhenova: Right now, our next task is to come up with a full guidelines update. ASCO have certain rules for the guidelines committee members. And so we are gearing for a full guideline update, which hopefully will be ready by the end of 2025. Brittany Harvey: Excellent. We'll look forward to that full update of the living guideline, and we'll still await results of these ongoing trials to further inform this living guideline. So I want to thank you so much for your work to rapidly and continuously update this living guideline, and thank you for the time today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: My pleasure. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store . If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

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Medically Integrated Dispensing Pharmacy: ASCO-NCODA Standards Update 25:05

27 weeks yang lalu25:05

25:05

Dr. Luis Raez and Michael Reff share the newest update to the medically integrated dispensing pharmacy standards from NCODA and ASCO. They review updates to domain one, on key patient-centered quality standards on health equity and social determinants of health, drug access, patient safety, education, and adherence to maximize treatment outcomes and domain two, on key operational quality standards on logistics, care coordination, and waste prevention. We also cover the impact of these updated standards for clinicians, oncology practices, and people receiving oral anti-cancer medications. Read the complete standards, " Medically Integrated Dispensing Pharmacy: ASCO-NCODA Standards ." Transcript These standards, clinical tools, and resources are available on ASCO.org. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the JCO Oncology Practice. Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts . My name is Brittany Harvey, and today I'm interviewing Michael Reff from the Network of Collaborative Oncology Development and Advancement and Dr. Luis Raez from Memorial Cancer Institute and Florida Atlantic University, co-chairs on "Medically Integrated Dispensing Pharmacy: American Society of Clinical Oncology – Network of Collaborative Oncology Development and Advancement Association Standards Update." Thank you for being here, Michael and Dr. Raez. Dr. Luis Raez: Thanks for inviting us. Michael Reff: Thank you for having us. Brittany Harvey: Then, before we discuss these standards, I'd like to note that ASCO takes great care in the development of its standards and ensuring that the ASCO Conflict of Interest policy is followed for each guidance product. The disclosures of potential conflicts of interest for the expert panel, including Michael and Dr. Luis Raez who have joined us here today, are available online with the publication of the standards in JCO Oncology Practice , which is linked in the show notes. So then, to dive into the content here, Michael, I'd like to start with what prompted an update to these ASCO-NCODA standards and what is the scope of this update? Michael Reff: Thank you, Brittany. What led NCODA and ASCO to endeavor in this, and it started back in 2019 as the amount of oral anticancer medications became more and more prevalent in cancer treatment, we saw the need providing a blueprint for excellence in care for patients prescribed oral anticancer medications, specifically in the outpatient setting. And the update was driven by the rapid growth of these oral oncolytics starting back in the mid to late 2015 through 2019 or so, and then continued on into the 2020s where we are today. We saw the increase in the complexity of the management of these patients with these therapies basically outside the traditional clinical settings. And we wanted to make sure that with more cancer treatments that are taken at home than just at the clinic, like in the oral setting, new challenges had emerged around patient safety, access, adherence, and overall treatment success. The updates now address patient-centered and operational interventions designed to improve access, safety, quality, accountability, and outcomes of oral anticancer and other supportive care medications prescribed for the cancer patient. Dr. Luis Raez: As Mike said, these guidelines help improve patient care tremendously, but also help us a lot as an oncologist, you know, community oncologists that- now that we have opportunity to dispense these oral oncolytics, we need help to create our medical integrated pharmacies, and NCODA is providing here a way that, how to do this safely, efficaciously, good quality, you know? So that's why I think we always do everything for the patients, but also this helps a lot to the doctors. And there are a lot of what we call specialty pharmacies or medical integrated pharmacies now nationwide. Michael Reff: I'll build on what Dr. Raez had mentioned. This is the impetus. If you looked at the innovation that was coming from the pharmaceutical companies, many of it coming in the oral form for anticancer medications, and based on that, taking a look at the infrastructure that is in place in these practices, whether it's in the community or the IDN or health system settings, this amount of innovation that was coming needed to be addressed by taking a look at the medically integrated oncology team. And these standards address not just the pharmacy component, but also the whole continuum of care, starting with a medical oncologist or the hematologist, with the pharmacists, nurses, the pharmacy technicians, others that are involved in the care of the patient. And there were no standards involved. And when we approached ASCO back in 2018 to eventually publish the first version of these standards, the need was identified, and we worked collaboratively with ASCO to create the first set and then the revisions as we talked about. One thing to note regarding the revision plus the original standards, we had a cross-section of the care team on the committee, and we did that very purposefully. So, the ASCO-NCODA team curated a committee to help develop these original standards and the revision of these standards with medical oncologists both from community and health systems, pharmacists from both community and health systems, and also nurses. And we also included a patient that currently has and currently receives oral anticancer medication. And so NCODA and ASCO are very proud of the committee that we put together because of the experts in their field, but also extended the invitation to a current patient. And we embedded everybody's expertise in the curation of these standards. Brittany Harvey: Absolutely. I appreciate that background and context and how it's critical to improve patient care. And these standards really help oncologists, and we're looking across the continuum of care to provide optimal care for our patients. So then next, Dr. Raez, I'd like to review the key points of the revised standards for our listeners. So for Domain 1, what are the key patient-centered quality standards on health equity and social determinants of health, drug access, patient safety, education, and adherence to maximize treatment outcomes? Dr. Luis Raez: Yeah, this was a great effort, you know, at the multidisciplinary team. And as you can read in the standard, there were more than 240 publications reviewed; more than 55 of them are quoted here. And the standards are in two groups, as you said. With the group one, I'll briefly mention some of them. For example, SDOH, social determinants of health, is very important because as doctors, we prescribe, and sometimes patients don't get the medication, you know? And we prescribe assuming that 100% of the patients will get the medication. But something simple like the patient doesn't have insurance, the patient is underinsured. I have a patient that we didn't have an address to send the medication because he's homeless. Something that as a doctor you say, "Oh, oh my God, this is outside my realm," but it's not outside reality. So that's why, even if we don't think that this is part of our expertise dealing with social determinants of health, the fact that the patients have food insecurity, they don't have transportation, they don't have insurance, they don't have a caregiver, impact tremendously in the outcomes of the therapy. So that's why, basically, in this standard, we want to call attention that SDOH, social determinants of health, needs to be identified. There are in the literature countless examples of why this is important. For example, in the guidelines, we quote two or three examples of prostate cancer studies that, for example, we quote a study of 27,000 people with prostate cancer that were taking oral oncolytics, and how come the fact that the elderly, seniors, the fact that they have high prescription costs, and how all of this affected the adherence to the medication. And that's why it's important to identify the SDOH. And in other sections of the guidelines, we said how to address them, no? Another important thing in this domain is the cultural, you know, we need to be culturally sensitive and to take care of all of these social factors. For example, here in South Florida, we deal with the Haitian culture, Filipino culture, Latin culture, and American culture, and it's a blend, but it's not easy to go from one to the other. Another one is the fact that we have to include new technologies. A lot of patients, for example, we use EMR, EMR Epic, and now Epic has everything in the phone. The fact that we can have now the patient can see her prescription medication over the phone, the fact that they can use the phone to request from you a refill, and from your phone, you send the refill to the pharmacy, and you notify from your phone to the patient that the refill is sent, and the patient can check in his phone that the refill is ready. These things are amazing because that's why it's important that we incorporate these technologies to the patient care, and in this specific case, of dispensation of oral therapies, no? Another crucial point is education. You cannot be sending a patient a package of 300 pills without education. So that's why in our guidelines, mainly pharmacy, clinical pharmacies, or in some centers like mine, we have advanced practice providers, it's mandatory in our centers to have like a one hour of education before you send the prescription. So the patient is aware about side effects and contraindications, all of these things. They provide them also materials and also consent. You know, in the old times, you don't give chemo without a consent. Now, a lot of people say, "Oh, it's only a pill." There is a lot of benefits or side effects that can come from the pill, so you need to consent everybody, you know? So, another aspect is adherence. I already told about that, but we need to provide patients with a baseline assessment, no? So, you cannot send again the prescription and hope, "Oh, I'll figure it out what happened next month when the patient comes back." I tell you, the patient is homeless, where are you going to send it? If the patient is telling you, "I don't have insurance," what good is it for you to send a prescription? The patient will not get it. So that's why you need to do a baseline assessment of adherence. You need to do a calendar. You need to do electronic support, I mentioned already with the EMR and the phones. For example, my MIP, my specialty pharmacist, sends me a message in the EMR, "Dr. Raez, the insurance is not covering, the patient has a high copayment, we are going to delay the dispensation of the medication." So there needs to be a communication. Or sometimes there is a confusion with the insurance, and I cannot wait for the poor patient to call three, four weeks later, "Oh, I didn't get the medication," to know what happened, no? My MIP is very good. They send the clinical pharmacist a message, "Hey, you know, the insurance doesn't believe that the pill is adequate, or you need to provide more documentation. You need to prove the mutation, the genetic aberration." So if you provide us that, the insurance may approve. So that communication with the doctor is very important to improve adherence. And one important thing that we have in this one that we didn't have in the anterior is the tracking of outside medications. A lot of times you say, "Okay, the insurance allowed us to provide the medication it's 100% responsible." But then the insurance says, "Oh, no, no, don't worry. CVS will provide the medication." So it says, "Well, it's you know, it's not my responsibility. CVS will provide the medication, they have to take care." But we know that outside our specialty pharmacies or MIPs, the care is not very good. So that's why we are taking our ownership that, "Okay, the insurance said the patient will get the medication from some outside pharmacy." But our clinical pharmacists track that. What happened? Did the patient get it? The patient didn't get it. The copayment is still high. So even if you get the medication from somewhere else, if the copayment is high, we, our clinical pharmacists, help the patient to navigate and get the foundation or the copayment or finally the maker, the industry partner, provides the drug for free, but somebody needs to do the paperwork. And that's why this is very important. We cannot abort our responsibility because, "Oh, the insurance said somebody else will give it." I work for the public healthcare system, so my patients, some of them don't have insurance, they are underinsured. So we see these problems every day. And finally, the standards talk about the importance of safety, documentation, verification, monitoring, refills, you know, you need to keep track of refills. We already mentioned how important is the technology to facilitate the refills, and the quality. Brittany Harvey: Yes, thank you for touching on those highlights for Domain 1. It's important that all patients have access to care and these oral anticancer medications, and not only just access to care, but safe and effective care. It's really important, as you mentioned, Dr. Raez, to meet patients where they're at and incorporate technology. And I also want to note the coordination with external pharmacies that you mentioned in tracking outside medications as well. It's not only important for multidisciplinary care within the oncology practice itself, but also external to the oncology practice. That's why we put together this multidisciplinary panel to develop these standards. So then, expanding on that, Dr. Raez, for Domain 2, what are the key operational quality standards? Those on logistics, care coordination, and waste prevention. Dr. Luis Raez: Yeah, we have a lot of standards here, but maybe we can summarize in five or six points, no? For example, financial toxicity in cost and waste are very important because the patients, yeah, you put them on therapy, but as you can understand, if there is disease progression, the patient don't need the medications. And sometimes you get refills even if the patient has disease progression. If you do a dose reduction, the same problem. Or you discontinue medication and the patient keeps getting the drugs. So, you're talking about drugs that are between 20 and 30 thousand dollars per month. This is a lot of money. There are studies that we're quoting in the standards that the waste could be from 1 to 3 or 4 thousand per patient, no? Another aspect is dispensing. When you dispense the medication, this is not as easy as, "I'll ship to your house a bag of medications." You know, there needs to be a diagram, a decision tree. You need to train the staff to know what we're doing. There needs to be an auditing of the process. They need to be even packaging and shipping, you know? For example, I'm in Florida today and outside in summer it's going to be 95 degrees. So, everybody leaves the package outside your house, and sometimes you go the whole day until when you come at 6:00 p.m. There are medications that cannot be left outside there, you know? I don't know, it sounds like a joke, but I have a patient that the medication used to be stolen because people thought that that was something important, you know? And of course, it's important because it's a $20,000 medication. So, the poor patient, because he lives in an area that is not safe, has to come and pick up in person. All of these things sound very trivial, but that's real life that affects adherence. Another important thing is shortage. This is something that we just suffered two or three years ago, and we have to think about what happens in the next shortage. What happens if there's going to be a shortage? What do we do or how are we going to do that? Now we know it's something that is happening probably very soon again, and something that we have to consider. Another standard is the care coordination. You need to have probably, if it's possible, a coordinator. I know that for small practices it's very hard, but for big cancer centers, you should have a coordinator of this. I already mentioned before, the communication between the physicians and the doctors to coordinate the care, no? You need to write the prescription again, you need to provide more information, or to be notified, "Hey, you know, the patient is throwing up in the first week, you need to see the patient, please," no? So, this type of communication needs to exist so we can serve the patient better. It's also important, you know, we're improving quality and we're improving care. It's important to try to collect patient-reported outcomes. This is something that now we have the opportunity, if we do things well, to do it and show that we're providing a better care. The other thing is that we already mentioned SDOH in the other standard. In this standard, we mention mainly SDOH to partner. For example, we collect in my center SDOH, and I always get frustrated when the patient doesn't have transportation. But I didn't know that there are local institutions that provide free Uber rides, free Lyft rides. So that's why it's important to partner with these institutions. I have a local grocery chain that provides free food for the patients, and I didn't know that. It's important to be aware what the patient needs and what resources do you have to fulfill the SDOH. That's the part that we mention in here. So that's why, in summary, those are the six probably most important points here. I'll ask Mike for some comments. Michael Reff: Thank you, Dr. Raez. Brittany, to answer your question, and as was pointed out on logistics, care coordination, and prevention of waste, certainly that is an aspect that has changed in the revision that we're here to talk about. There's really two components to waste, and it's cost avoidance and then waste prevention. And as Dr. Raez mentioned several times, the importance of the medically integrated team and having the ability for that practice to fill that prescription internally and have robust documentation. Cost avoidance is a critical component that the medically integrated pharmacy, or the MIP, can help the total cost of care. And that is by preventing errant fills or waste that can occur by intervening in the care of the cancer patient, as we do every day. But when the practice has access to the medication and can fill that prescription in-house in the medically integrated pharmacy, that team, that care coordination that takes place, can prevent those errant fills or additional fills when there's dose reductions, there's holidays, there's things that happen in real time. And it's impossible for a mail-order pharmacy that's in another state that has lead times, when a prescription needs to be mailed 7 days or 10 days before the patient will run out of the medication, it's impossible for them to logistically coordinate that care like we can internally within the medically integrated pharmacy. So, we prevent waste and overall cost of care by cost avoidance and having that coordination or that continuity of care that we talk about. And we prevent waste from the mail-order pharmacies by taking that prescription internally and filling it, but also doing it in a way that's more sustainable and cost-effective for all stakeholders in the oncology ecosystem. Brittany Harvey: Absolutely. Thank you both for reviewing those key standards for Domain 2 and touching on the importance of distribution logistics and all the things that a medically integrated pharmacy needs to think through in getting oral anticancer agents to patients. Following that, Michael, we've touched on this a little bit earlier, but how will these updated standards impact clinicians and oncology practices? Michael Reff: Yes, and as Dr. Raez and I have discussed throughout this podcast, these additional standards are there to help support that continuity of care by educating the clinicians that are in the oral anticancer medication space to elevate their provision for these oral therapies. What I mean by that is the practice has to perform at a certain level in order for them to, as I call it, deserve the right to fill that prescription by having the processes and procedures in place. And these standards, these updated or revised standards, are the blueprint for better patient care and to help the practices execute on that journey of continuous improvement. Dr. Luis Raez: Yeah, I only want to add, we have practical examples in the guidelines. We quote a couple of studies that have been successful. And this year, for example, I am a lung cancer doctor, we are presenting in World Lung our standards of adherence to oral oncolytics for EGFR therapy, following the NCODA-ASCO standards. We're around 95% of adherence. We are a healthcare system that is public. We have people with no insurance and a lot of social determinants of health. We are trying to show that it's feasible, even in the most difficult circumstance, when you follow the standards, to be successful. Brittany Harvey: Definitely, these standards can help clinicians and oncology practices succeed in providing these medications. So then beyond that, and to wrap us up, Michael, what do these revised standards mean for patients who are receiving oral anticancer medications? Michael Reff: Yes, great point and question, Brittany, because we have covered the benefits to the clinicians and the practices themselves. But how is this going to support better patient care? And it does it in a whole host of ways. I'll cover just a few of them. What I'm about to share with you relates back to what we call at NCODA the "core claims." Like, what's the core claims of having a medically integrated pharmacy within the practice? And there are seven different core claims that we feel practices that are focused on the continuity of care can deliver better outcomes that are embedded in these standards. And it's talking about abandonment, adherence, access and affordability, speed to therapy or time to fill, as we call it, education, patient satisfaction, and cost avoidance that we covered earlier. So those are the core claims that a practice that follows these revised standards can help elevate. So, faster and more affordable access to the oral cancer medications; individualized support to address barriers like transportation, finance, language, or health literacy, and so on; clear, patient-friendly education; something that is near and dear to all clinicians' hearts, and of course, the patient that was on our panel or on our committee, to empower them to manage side effects and recognize when to seek help; and a stronger partnership with a care team, with regular follow-ups focused on their experience, challenges, and successes; and then, greater overall safety through proactive monitoring for medication errors or complications. So all of these aspects, or tenets, as I'll call them, are baked into these quality standards that are totally aligned with NCODA's core claims document that, again, talks about abandonment, adherence, access and affordability, speed to therapy, education, satisfaction for the patients, and also cost avoidance. Dr. Luis Raez: I only want to add and invite the community to adhere to these standards, to practice the standards. You will be providing the best patient care that we can nowadays. Brittany Harvey: Definitely. I think these standards are very important. And Michael, I thank you for touching on those key claims from NCODA. I think those, along with these updated standards, will improve outcomes for patients everywhere. So I want to thank you both so much for your work to update these standards and all the time you put into it. And thank you for your time today too, Michael and Dr. Raez. Michael Reff: I'd like to thank not only the committee, my esteemed committee that helped support the standards and the revision. Many of the original healthcare providers and patient that were on the first go of the standards were part of the second standards. We revised it, of course, and we got additional support from the new committee. And certainly ASCO and their partnership and collaboration with NCODA has been tremendous. And we look forward to the oncology community at large adopting these standards, again, to work together, we do become stronger, and it will improve cancer care for patients receiving oral anticancer medications. So thank you, Brittany. Dr. Luis Raez: I only want to say the same thing. Actually, there is probably more people in NCODA that is not in the publication that has helped. Same in ASCO. Also, we want to give thanks to Dr. Stephen Grubbs, our leader in quality. He's retiring. We're going to miss him, but he has been a key collaborator with Mike organizing these standards for the last five or six years. So, looking forward to these standards in practice. Brittany Harvey: Absolutely. A big thank you to the entire panel and everyone who contributed to this, and NCODA as well. And then finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the complete standards, go to www.asco.org/standards . I also encourage you to check out the companion episode on these standards on the PQI podcast by NCODA , which you can find on Apple Podcasts and Spotify. You can also find many of our standards and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

1
Symptom Management for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors Guideline 19:20

29 weeks yang lalu19:20

19:20

Dr. Kimberly Perez and Dr. Jaydira Del Rivero discuss the new guideline from ASCO on symptom management for well-differentiated GEP-NETs. They share the latest recommendations on managing symptoms related to hormone excess, including carcinoid syndrome and carcinoid heart disease, managing symptoms of functioning pancreatic neuroendocrine tumors, and also palliative interventions. Dr. Perez and Del Rivero share how to use this guideline in concert with the systemic therapy for tumor control in metastatic well-differentiated GEP-NETs guideline, and hope for the future for the treatment of gastroenteropancreatic neuroendocrine tumors. Read the full guideline, " Symptom Management for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline. " Transcript This guideline, clinical tools, and resources are available on ASCO.org . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in JCO Oncology Practice . Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast , one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts . My name is Brittany Harvey and today I'm interviewing Dr. Kim Perez from Dana-Farber Cancer Institute and Dr. Jaydira Del Rivero from the Center for Cancer Research at the National Cancer Institute, co-chairs on "Symptom Management for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline." Thank you for being here today, Dr. Del Rivero and Dr. Perez. Dr. Kim Perez: Thank you. Dr. Jaydira Del Rivero: Thank you so much for the invitation. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Perez and Dr. Del Rivero, who have joined us here today, are available online with the publication of the guideline in JCO Oncology Practice , which is linked in the show notes. So then to jump into the content here, first Dr. Del Rivero, could you provide an overview of the scope and purpose of this guideline? Dr. Jaydira Del Rivero: Yeah. Thank you so much. Well, first, we really wanted to thank ASCO for allowing us to develop these guidelines for the management of gastroenteropancreatic neuroendocrine tumors. I do want to mention that there is also another set of guidelines that I was very fortunate also to co-chair with Dr. Perez on the systemic management of gastroenteropancreatic neuroendocrine tumors. But when discussing these guidelines as well as with the different panelists, experts in this type of disease, we also realized that the management of these tumors are quite complex, not only from the management of the disease progression, but at the same time, management of the symptoms related to the hormone excess. And because of that, we like to thank ASCO for allowing us to then not only have a discussion on the systemic management of these tumors, but at the same time develop recommendations for the symptoms related to the different hormones that these neuroendocrine tumors may produce. These guidelines are for the management of grade 1 to grade 3 metastatic gastroenteropancreatic neuroendocrine tumors. These guidelines include the management of the different aspects and the symptoms related to hormone excess, such as carcinoid syndrome, carcinoid heart disease, how to manage carcinoid crisis, as well as the different symptoms and how to manage the functional pancreatic neuroendocrine tumors and as well as provide recommendations in the different treatments for these tumor types, not only from the systemic management but also from the surgical management as well as for liver-directed therapy options and the different aspects in terms of the palliative care of these patients to improve not only the symptoms related to the hormone excess caused by these tumors, but as well as to improve the quality of life. Brittany Harvey: Absolutely. And I appreciate that overview. And yes, we'll link the guideline on the Systemic Therapy for Tumor Control for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors in the show notes for our listeners so that they can refer to that companion guideline as well. So then you just described the several different categories of recommendations that this guideline covers on symptom management. So, Dr. Perez, I'd like to start reviewing some of those key recommendations of that guideline. So, starting with what are the key recommendations for carcinoid syndrome and carcinoid heart disease? Dr. Kim Perez: Thank you Brittany. Yeah, I also want to thank ASCO for inviting us to do this podcast today. Just to start, I think these guidelines will really add to what's available in the literature to provide a kind of a quick look for the community provider to manage carcinoid-related symptoms. I think the highlights that I would point out are we've all been using somatostatin analogs for the last few decades to manage symptoms, but with the newer treatments that are now available, we tried to highlight what does the literature support in regards to PRRT, what does the literature support in regards to using systemic therapy for disease management, but also the benefits that you will get from a symptom management perspective using other modalities. I think the highlight really is it's a multidisciplinary approach. We are now considering surgery and embolization or interventional radiology as a critical piece. And I think the third that I'd highlight is the fact that sometimes we get too focused on carcinoid syndrome and the symptoms will actually, may result from other things. And the highlight in the algorithms that we've provided is what other things cause carcinoid-related diarrhea. And let's not forget about that because we will find ourselves treating and patients getting very frustrated with persistence of symptoms when in actuality, we should be treating something else that is causing a very similar symptom. For carcinoid heart disease, I think there are more and more guidelines that are now available to provide guidance there, but I think the major advances are that we should be utilizing heart assessment with echocardiogram with lab values such as BMP. But also critical to this is consulting with our cardiology colleagues and making sure that we're identifying heart related issues that are resulting from hormone excess sooner than later because interventions on the earlier side can really make a significant impact on quality of life and associated comorbidities and mortality. Brittany Harvey: Thank you for reviewing those key points for both carcinoid syndrome and carcinoid heart disease symptom management. So then the next set of recommendations. Dr. Del Rivero, what are the key highlights for symptom management of functioning pancreatic neuroendocrine tumors? Dr. Jaydira Del Rivero: Yes, it's very important to recognize the symptoms related to hormone excess due to pancreas neuroendocrine tumors. Up to 10% of pancreas neuroendocrine tumors may produce different hormones. Among those hormones can be insulin, gastrin, glucagon, somatostatin. So it's important to know and understand that based on what a neuroendocrine tumor is, they may produce different types of hormones. The importance of these guidelines is to also recognize some of these symptoms and how to address that, because it's not necessarily in these tumor types besides the management of metastatic disease, and know the different options that we recommend for metastatic disease from the systemic therapy, such as chemotherapy or targeted therapies or PRRT. It's important to recognize the symptoms because based on the symptoms we may recommend a different approach. That's something that is important to acknowledge and recognize. Moreover, in certain functional pancreas neuroendocrine tumors, as Dr. Perez mentioned, is a multidisciplinary approach. And it's important to also discuss these different cases with your endocrinologist. You may need to have an experienced endocrinologist to manage, for example, the excess of insulin. And also discuss your cases with a surgeon and interventional radiologist because some of these approaches can certainly improve the symptoms related to hormone excess. I understand that sometimes medical oncologists in the communities may not have access to the multidisciplinary approach or have the different teams that can manage these tumors, and that's the reason why with these guidelines we wanted to establish the understanding of different symptoms associated with the hormone excess to these neuroendocrine tumors as well as how to manage this. For example, in the case of insulinoma, I think for the medical oncologist it is important to know that the everolimus is an option to be used for these tumors, not only to manage tumor progressions related to this tumor type at the same time, because everolimus as a side effect causes hyperglycemia, that can also improve some of the symptoms related to the excess of insulin besides the somatostatin agonist. I think these recommendations will allow the medical oncologist to recognize the symptoms and based on what the symptoms cause, then you can have a different approach that could be added to the systemic therapies options as well. Brittany Harvey: Yes, beyond systemic therapy, it's important to be recognizing symptoms to provide an individualized approach for every single patient. So then, following that overview of symptom management for functioning pancreatic neuroendocrine tumors, Dr. Perez, what is recommended regarding palliative interventions for patients with gastroenteropancreatic neuroendocrine tumors? Dr. Kim Perez: Yeah, great question. So I think what's unique to neuroendocrine tumors is that the palliative approach really mirrors what we would be doing for symptom management. Some of these patients are living a very long time with carcinoid related symptoms. And so the approach that we take for the carcinoid symptom control is going to mirror the palliative piece of it. I think for those who develop a burden of disease related symptoms, I think it mirrors what we do across the board for all cancer-related complications. And so I think what we attempted to highlight here and included one of our colleagues who focuses specifically on the field of palliative care and neuroendocrine tumors, was to never really lose sight of what we've been doing to care for symptom management throughout the patient's journey and to always rereview the etiology of the symptoms, ensure that we don't focus solely on carcinoid-related issues, but also the symptom management that we would apply to all patients with cancer-related burden symptoms. Brittany Harvey: Definitely. I think that's a helpful approach to consider when thinking about how to manage these palliative interventions as well. So then Dr. Del Rivero, what should clinicians know as they implement these symptom management recommendations? Dr. Jaydira Del Rivero: Yes, thank you so much for that question. As we have discussed in the last 10 or 15 minutes, we have discussed the different approaches on the management of gastroenteropancreatic neuroendocrine tumors. Clinicians, I think it's important to know that neuroendocrine tumors is a quite complex disease because we're not only addressing the management of tumor growth, but we're also addressing the management of the symptoms related to hormone excess and the complexity associated with that. When medical oncologists or clinicians implement these recommendations it's to understand what symptoms these tumors may cause related to the hormone excess but at the same time, how do we approach those symptoms? As Dr. Perez said that I think is very important is to recognize the different types of diarrhea. It doesn't mean that if the patient has worsening diarrhea, it doesn't mean that this is related to disease progression. So it's important to recognize so that way you can address that, because the type of diarrheas can be related because of the lanreotide or somatostatin agonist, it could be because of the prior surgery. I think it's important to recognize those in order to address the symptom. And the same with the gastroenteropancreatic neuroendocrine tumors. It's important to know what hormones they produce because there are different measurements that may be added to the systemic management of these tumors. I think that there are two aspects here, and that's the reason why these guidelines were implemented in the sense that not only we're going to manage disease progression of these tumors, or how do we manage the metastatic disease of these tumors, but at the same time, how do we manage the symptoms related to the hormone excess and the different complications. Moreover, I think, as we discussed earlier, we need to manage these tumors in a multidisciplinary approach. And something very important is not like one size fits all, because the treatment recommendations, it will depend on different characteristics in terms of the tumor presentations. And hormone excess is one of the important aspects to recognize so that way we can implement these recommendations that will definitely help the quality of life of these patients. Brittany Harvey: Absolutely. And using these guidelines in concert with the systemic therapy guidelines is key. And then beyond this impact for clinicians that Dr. Del Rivero has just outlined, Dr. Perez, what does this new guideline mean for patients with gastroenteropancreatic neuroendocrine tumors? Dr. Kim Perez: Yeah, I think that's an important highlight of this guideline. It really gives patients a voice. I think it recognizes the fact that these symptoms can go unmanaged or mismanaged or just missed, and patients commonly will come in feeling very frustrated and feeling very ill. And I think it will provide them a means to open up a conversation with their providers and say, "Hey, this is what I'm experiencing. Let's talk about what's available. How does this apply to me?" And I think that can be very empowering. I think it's really hard nowadays with so many sources and resources online and patients are really left wondering what are the bullet points that they should be bringing to their clinician appointments? And I think that these guidelines provide them a good framework for those discussions. Brittany Harvey: Yes, bringing these discussion points for patients is very important to be able to have those resources. And we have some patient resources and information available on the website for this guideline and we can link that in the show notes for listeners. So then you've both touched on the importance of this guideline for improving quality of life and we continue to see advancements in this field. So Dr. Del Rivera, what are the outstanding questions regarding symptom management and tumor control for gastroenteropancreatic neuroendocrine tumors? Dr. Jaydira Del Rivero: I have to say whenever somebody asks me that question, the word that I will say is I feel hopeful, because more than 10 years ago we didn't have that many options for gastroenteropancreatic neuroendocrine tumors. And it has been in the last decade or so that there has been more developments in the management of these tumors as well as the understanding of the symptoms related to these tumors. But that said, yes, we do need more therapies for gastroenteropancreatic neuroendocrine tumors. Of the treatment options that we have, we all know in the field that even though we have disease control by using the different options for the systemic management of gastroenteropancreatic neuroendocrine tumors, we need options where we can achieve an objective response, especially for these tumor types. But there is a significant volume of disease and we see a lot of these patients with gastroenteropancreatic neuroendocrine tumors. And now where the field is going is to make some of these therapies more effective, to develop more therapies as well. For example, immunotherapies, a different type of immunotherapy understand the tumor immune microenvironment of these tumors in order to develop therapies as well. From the antibody drug conjugates, I think that's a new way to also address or treat these tumor types, understanding about the different markers found on these tumors that way they can be addressed in different ways. Now with the development of new therapies, I think that's something that can help us as well not only have disease control and as well as having an objective response, but having a better objective response can certainly also help with the symptoms related to hormone excess too. In terms of other therapies, I think some of the issues that we encounter are like the refractory carcinoid diarrhea and how do we manage this. We do have therapies that can help us control the diarrhea in the refractory settings, such as telotristat. Telotristat is one of the newer medications that can help us control the refractory diarrhea. But that said, despite this, that we still encounter situations where it's sometimes difficult to control. I think in those situations it will be good to understand more about the biology of these tumors as well and how we manage. If there is a different time or how do we implement these options. I think there is so much to learn. But that said, I feel we're in hopeful times. We're understanding more about these tumors so that way we can help us develop better therapies not only to have control of the tumor growth as well having control of the symptoms. And it's the same with the pancreas neuroendocrine tumors in the metastatic setting. Sometimes it may be difficult to control this hormone excess. But understanding these and having therapies that can achieve more of an objective response, I think that will definitely help us more and manage these patients. But one aspect I want to mention, and Dr. Perez also mentioned as well, the fact that we have these guidelines that help us understand about the different symptoms related to hormone excess and how to address it, I think is very important because having symptoms related to hormone excess can be detrimental to the quality of life on patients with neuroendocrine tumors that may necessarily be related to disease progression and having this information is so important. And I'm hopeful for the different therapies. There's different clinical trials ongoing for neuroendocrine tumors and especially in the field of PRRT. And a lot of more information will come with the different alpha-PRRT and combination therapy. So more information to come in the next couple of years. So this is, in my opinion, hopeful times for this field. Brittany Harvey: It's great to hear that you're hopeful for all the developments in this field and we'll look forward to the development and discovery of new therapies and further research and then, hopefully incorporate those updates into guidelines in the future. So I want to thank you both so much for your work to develop these guidelines and thank you for your time today. Dr. Del Rivero and Dr. Perez. Dr. Jaydira Del Rivero: Thank you so much for having us. Dr. Kim Perez: Thank you. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

1
Systemic Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer Guideline Update 22:48

30 weeks yang lalu22:48

22:48

Dr. Rohan Garje shares the updated recommendations for the ASCO guideline on systemic therapy for patients with metastatic castration-resistant prostate cancer. He discusses the systemic therapy options for patients based on prior therapy received in the castration-sensitive and non-metastatic castration-resistant settings. He emphasizes personalizing treatment choices for each individual, considering patient-specific symptoms and signs, treatment-related toxicities, potential drug interactions, cost, and access. He also reviews recommendations on response assessment. The conversation wraps up with a discussion of potential future updates to this guideline, as the guideline transitions into a "living guideline" on mCRPC. Read the full guideline update, " Systemic Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Update ". Transcript This guideline, clinical tools, and resources are available at www.asco.org/genitourinary-cancer-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology . Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast , one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts . My name is Brittany Harvey and today I'm interviewing Dr. Rohan Garje from Miami Cancer Institute Baptist Health South Florida, lead author on, "Systemic Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Update." Thank you for being here today, Dr. Garje. Dr. Rohan Garje: Absolutely. Thank you so much for having me, Brittany. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Garje, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology , which is linked in the show notes. So then, to start on the content of this guideline, first, could you provide us an overview of the purpose of this guideline update? Dr. Rohan Garje: Sure. So ASCO has guidelines for prostate cancer and the specific guideline which we have updated for metastatic castrate-resistant prostate cancer was originally published in 2014. It's almost a decade. It's been a long time due for an update. Over the last decade, we have seen a lot of advances in the treatment of prostate cancer, specifically with regards to genomic testing, newer imaging modalities, and also the treatment landscape. Now we have newer options based on genomic targets such as PARP inhibitors, we have radiopharmaceuticals, a newer variant of chemotherapy, and also some specific indications for immunotherapy which were not addressed previously. Because all these advances have been new, it was really important for us to make an update. In 2022, we did make a rapid update with lutetium-177, but these additional changes which we have seen made it an appropriate time frame for us to proceed with a newer guideline. Brittany Harvey: Absolutely. It's great to hear about all these advances in the field to provide new options. So I'd like to next review the key recommendations from this guideline. So let's start with the overarching principles of practice that the panel outlined. What are these key principles? Dr. Rohan Garje: As a group, all the panel members came up with some ground rules: What are necessary for all our patients who are being treated for metastatic CRPC? First, the founding aspect was a definition for what is metastatic CRPC. So we defined metastatic CRPC as castrate level of testosterone with evidence of either new or progressive metastatic disease on radiological assessments or patients who have two consecutive rising PSAs in the setting of existing metastatic disease. We also emphasized on the need for germline and somatic testing for patients with metastatic prostate cancer at an earliest available opportunity because it is critical to select appropriate treatment and also right treatment for patients at the right time. And we actually have a concurrent guideline which addresses what genes to be tested and the timing. The other principles are patients should continue to receive androgen deprivation therapy or undergo surgical castration to maintain castrate level of testosterone. Now the key aspect with these guidelines is personalizing treatment choices. As you can see the evolution of treatment options for prostate cancer, the drugs that were initially developed and approved for prostate cancer were primarily in castrate-resistant settings, but now most of these drugs are being utilized in castrate-sensitive. So, when these patients develop castration resistance, the challenges are there are no appropriate particular drug-specific guidelines they meet. So, it's very important for the clinicians to be aware of what treatments have been received so far prior to castration resistance so that they can tailor the treatment to patient specific situations. In addition, prior to choosing a therapy, it is important for the physicians to consider patient specific symptoms or signs, treatment-related toxicities, potential drug interactions, cost, and also access to the drugs. There may be multiple treatment options available for the patients, but for a patient specific scenario, there may be a drug that may be more promising than the others. So, it is important to tailor the drug choices based on patients' unique circumstances. The panel also recommends to early integrate palliative and supportive care teams for symptom management and also discuss goals of care with the patient as each patient may have unique needs and it's important for physicians to address those concerns upfront in the care. The panel also suggests patients to receive RANK ligand inhibitors such as denosumab or bisphosphonates such as zoledronic acid to maintain the bone strength to prevent skeletal-related events. Finally, I would like to also emphasize this point about the lack of randomized clinical trial data for optimal sequencing of therapies for patients with metastatic CRPC. As I previously alluded, we have taken into account all ongoing clinical trials, prior published data, and came up with a format of preferred drugs based on prior treatments and, I think, by following these several clinical principles which I just mentioned, we can optimally choose and utilize best treatments for patients with metastatic CRPC. Brittany Harvey: Absolutely. These principles that you just outlined are important for optimal patient care, and then I want to touch on one of those things. You talked importantly about the treatments received so far. So in the next set of recommendations, the role of systemic therapy was stratified by the prior therapy received in the castration-sensitive and non-metastatic castration-resistant setting. So starting with what does the panel recommend for patients who are previously treated with androgen deprivation therapy alone in these previous settings and whose disease has now progressed to metastatic castration-resistant prostate cancer? Dr. Rohan Garje: There are multiple treatment options based on prior treatment received. So for patients who received only ADT for their castration-sensitive disease, the panel strongly urges to get HRR testing to check for homologous recombinant repair related changes, specifically for BRCA1 and BRCA2 mutations, because we have three studies which have really shown significant clinical benefit for patients who have BRCA1 and BRCA2 mutations with drugs such as the combination of talazoparib and enzalutamide or olaparib with abiraterone or niraparib with abiraterone. Unless we test for those mutations, we'll not be able to give these agents upfront for the patients. In the HRR testing, if patients have HRR alterations but they are in genes which are non-BRCA, the guideline panel recommends to utilize talazoparib and enzalutamide based combination therapies. Now, if they don't have HRR alterations then there are multiple treatment choices available. It could either include androgen receptor pathway inhibitors such as abiraterone with prednisone. We could also consider docetaxel chemotherapy. The alternate choices for androgen receptor pathways include enzalutamide or the newer agents such as apalutamide and docetaxel. So, as you can see there are multiple options available, but the panel definitely emphasizes to test for HRR testing because this gives patients access to more precision therapies at this point. There may be various scenarios where a unique drug may be available for a specific patient situation. For example, patients who have very limited disease burden and may have one or two metastatic lesions, after a multidisciplinary discussion, targeted local therapies such as radiation or potentially surgery could also be offered. In select patients who have very indolent disease where they are castrate-resistant based on slow rising PSA, low-volume disease or asymptomatic disease can consider sipuleucel-T. And in patients who have bone-only metastatic disease, we could also consider radium-223, which is primarily now utilized for patients who have symptomatic bone disease. Brittany Harvey: Great. I appreciate you reviewing all those options and talking about how important it is to tailor treatment to the individual patient. So then the next category of patients, what is recommended for those who have been previously treated with ADT and an androgen receptor pathway inhibitor and whose disease has now progressed to metastatic castration-resistant prostate cancer? Dr. Rohan Garje: So for patients who received ADT along with an androgen receptor pathway inhibitor, which we consider would be a most common cohort because most patients now in castration-sensitive setting are receiving androgen receptor pathway inhibitor. It was different in the past where five or six years back ADT alone was the most common treatment, but fortunately, with enough awareness and education, treatment choices have improved. Patients are now receiving ADT and ARPI as the most common choice of drug. Once again, at this point the panel emphasizes to consider HRR testing in there is enough data for us to suggest that patients who have alterations in the HRR pathway definitely will benefit with the PARP inhibitor. You know the multiple options, but specifically we speak about olaparib. And then if they are HRR-negative, we prefer patients receive agents such as docetaxel or if they are intolerant to docetaxel, consider cabazitaxel chemotherapy, options such as radium-223, and if they have a specific scenario such as MSI-high or mismatch repair deficiency, pembrolizumab could also be considered. The panel also discussed about the role of a second ARPI agent. For example, if patients progressed on one androgen receptor pathway inhibitor, the second androgen receptor pathway inhibitor may not be effective and the panel suggests to utilize alternate options before considering androgen receptor pathway inhibitor. There may be specific scenarios where a second ARPI may be meaningful, specifically, if alternate choices are not feasible for the concern of side effects or toxicities or lack of access, then a potential ARPI could be considered after progression on ARPI, but the panel definitely encourages to utilize alternate options first. Brittany Harvey: Great. Thank you for outlining those options as well for those patients. So then the next category, what is recommended for patients who have been previously treated with ADT and docetaxel? Dr. Rohan Garje: For patients who received ADT and docetaxel and were never treated with androgen receptor pathway inhibitors, the panel again emphasizes on HRR testing. If they have BRCA1 and 2 mutations, the combination therapies of talazoparib with enzalutamide, olaparib with abiraterone, or niraparib with abiraterone are all good choices. If they don't have BRCA mutations but they have other HRR mutations, the panel suggests to potentially utilize talazoparib with enzalutamide. And if they do not have any HRR alterations, the options could include androgen receptor pathway inhibitors such as abiraterone or enzalutamide. I want to emphasize that these are preferred options, but not the only options. As you can see, there are multiple options available for a particular clinical situation - so the ability of the physicians to access particular combinations, the familiarity of those drugs or the patient's unique situation where they have other medications which can potentially interact with a choice of agents. So I think based on access, based on cost and patients' concurrent illness with potential drug interactions can make one particular combination of therapy better over the other options. Brittany Harvey: Absolutely. That's key to keep in mind that access, contraindications, and cost all play a role here. So then the next set of recommendations. What are the key recommendations for patients who have previously been treated with ADT, an androgen receptor pathway inhibitor, and docetaxel who now have mCRPC? Dr. Rohan Garje: Yes. In this group, the options remain, again, broad. We utilize PSMA imaging here specifically and if they are positive on PSMA imaging, lutetium-177 is a good option. If they do not have PSMA-positive disease on PSMA imaging but if they have HRR alterations, olaparib could be utilized. And if they are negative on PSA imaging, they don't have HRR alterations, then alternate options could include cabazitaxel, radium-223. And if they have MSI-high or deficiency in mismatch repair, pembrolizumab could be utilized in this setting. Brittany Harvey: Thank you for outlining those options as well. So then next the panel addressed treatment options for de novo or treatment emergent small cell neuroendocrine carcinoma of the prostate. What are those key recommendations? Dr. Rohan Garje: Yes. This is a very high unmet need group because there are limited clinical trials, especially prospective clinical trials addressing treatment options for this group. Most of our current guidelines are always an extrapolation from lung small cell cancer based guidelines, but the panel recommends to utilize cisplatin or carboplatin along with etoposide as a preferred choice for this group. Also, an alternate option of carboplatin along with cabazitaxel could be considered for this cohort. The panel also encourages participation in clinical trials. There are numerous trials ongoing now in smaller phase studies and I think it's important for patients to consider these trials as well, because this will give them access to newer agents with potential biological targets. In addition to these agents in specific scenarios or potentially case by case basis, because we don't have prospective data, so we have made it as a select case by case basis to consider adding immunotherapy along with platinum-based chemotherapy followed by maintenance immunotherapy, which is currently a standard of care in small cell lung cancer. But the data is so limited in prostate cancer, so the panel suggested that it has to be a case by case basis only. The alternate options also include lurbinectedin, topotecan, tarlatamab upon progression on platinum-based chemotherapy. Brittany Harvey: Yes. It's important to have these recommendations in these unique situations where there is really a lack of data. So then the final set of recommendations I'd like to cover, what does the panel recommend for how clinicians should assess for response while patients are on systemic therapy and what scans are recommended for this response assessment? Dr. Rohan Garje: Yes. Again, this is another strong emphasis of the panel for global assessment of the patients. Traditionally, patients and physicians per se are heavily reliant on PSA as an accurate marker for response. This is in fact true in earlier phases of prostate cancer either in castrate-sensitive setting or localized prostate cancer setting. But as patients evolve into castrate-resistant, we don't want to heavily rely on PSA alone as a marker of response. The panel suggests to incorporate clinical response, radiological response, and also include PSA as a component, but not just rely primarily on PSA. So the panel also suggests that patients should get a bone scan and a CT scan every three to six months while on treatment to assess for appropriate response or for progression. And now one key important aspect, we are all aware about the evolving role of PSMA-based imaging with several of these new agents that are currently available. We do acknowledge these scans definitely have an important role in the care for patients with metastatic prostate cancer. Currently, the utility is primarily to select patients for lutetium-based therapy and also in situations where the traditional scans such as technitium 99 bone scan or CT scan are equivocal, then a PSMA-based imaging can be helpful. Now we are also aware that there are newer studies coming up, prospective data coming up for the role of PSMA-based imaging for response assessment. We are hoping to update the guidelines if we get access to newer data, but currently we have not recommended the utility of PSMA-based imaging for response assessments. Brittany Harvey: Understood. And I appreciate you describing where there is data here and where there's a lack of data to currently recommend. And we'll look forward to future updates of this guideline. Coming back to – at the start you mentioned how much has changed since the last guideline update. So Dr. Garje, in your view, what is the importance of this update and how will it impact both clinicians and patients with metastatic castration-resistant prostate cancer? Dr. Rohan Garje: The updated guidelines are designed to have a significant impact on clinical practice and also patient outcomes by providing clinicians with a comprehensive evidence-based framework for managing patients with metastatic CRPC. And also, by using these guidelines can make informed decisions, can select therapies tailored to patients' unique genomic status, clinical situation, where they are in the course of the cancer based on what they received previously. Also utilizing these guidelines, we can potentially improve patient outcomes, improve survival, and importantly have efficient use of healthcare resources. Brittany Harvey: Absolutely. We're always looking for ways to improve patient outcomes and survival. I want to wrap us up by talking a little bit about the outstanding questions in this field. So earlier you had mentioned about prospective data to come about PSMA PET scans, but what other outstanding questions are there for patients with metastatic castration-resistant prostate cancer? And what evidence is the panel looking forward to for future updates? Dr. Rohan Garje: We do have now rapidly evolving data specifically about the utility of the radiopharmaceutical lutetium-177 prior to chemotherapy. We are hoping that with newer data we can make some changes to the guideline based on that. We are also looking at newer drugs that are coming up in the pipeline, for example, androgen receptor degraders. We are looking at data that might potentially help based on bispecific T-cell engagers and newer radiopharmaceuticals. So I think in the next few years, we will definitely update all the guidelines again. But this time we are trying to do it more proactively. We are following a newer model. We are calling it as 'living guidelines' where we are actually utilizing week by week updates where we look at the literature and see if there is any potential practice impacting change or publication that comes up. And we are trying to incorporate those changes as soon as they are available. That way patients and practicing physicians can get the latest information available through the guidelines as well. Brittany Harvey: That's great to hear. Yes, we'll await this data that you mentioned to continuously update this guideline and continue to improve patient outcomes for the future. So Dr. Garje, I want to thank you so much for your time to update this guideline. It was certainly a large amount of recommendations, and thank you for your time today, too. Dr. Rohan Garje: Thank you so much for having me here. And it's always nice talking to you. Brittany Harvey: And finally, thank you to our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/genitourinary-cancer-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

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Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Rapid Update 9:22

31 weeks yang lalu9:22

9:22

Dr. Nimish Mohile and Dr. Jaishri Blakeley share the new rapid recommendation update to the therapy for diffuse astrocytic and oligodendroglial tumors in adults guideline. They review the evidence from the INDIGO trial that prompted this update, and how to incorporate the use of vorasidenib into clinical practice. They discuss the importance of molecular testing, particularly for IDH1 or IDH2 mutations and outstanding questions for treatment of patients with oligodendrogliomas and astrocytomas. Read the latest update, " Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline Rapid Recommendation Update ." Transcript This guideline, clinical tools, and resources are available at http://www.asco.org/neurooncology-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in Journal of Clinical Oncology . Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts . My name is Brittany Harvey and today I'm interviewing Dr. Jaishri Blakeley from Johns Hopkins University School of Medicine and Dr. Nimish Mohile from the Department of Neurology and Wilmot Cancer Institute at the University of Rochester Medical Center, co-chairs on "Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: American Society of Clinical Oncology-Society for Neuro-Oncology Guideline Rapid Recommendation Update." Thank you for being here today, Dr. Blakeley and Dr. Mohile. Dr. Jaishri Blakeley: Thank you. Dr. Nimish Mohile: Thank you for having us. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Blakeley and Dr. Mohile who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology , which is linked in the show notes. So then, to jump into the content here, Dr. Mohile, could you start us off by describing what prompted this rapid update to the ASCO-SNO therapy for diffuse astrocytic and oligodendroglial tumors in adults guideline, which was previously published in 2021? Dr. Nimish Mohile: Yeah. So the key reason for this update is the publication of a study in 2023. And this was a study called the INDIGO study that looked at a new class of therapies, something called IDH inhibitors. And in this study with a drug called vorasidenib, changed how we think about the treatment of oligodendrogliomas and astrocytomas, so particularly the grade 2 oligodendrogliomas and grade 2 astrocytomas. Because of the results of that study, we decided that we needed to do an update to inform clinicians about some of these changes and how we might approach these tumors differently today. Brittany Harvey: Great. I appreciate that background. So then, based off the new data from the INDIGO study, what are the updated and new recommendations from the expert panel? Dr. Nimish Mohile: So the key findings from the INDIGO study involved people who had grade 2 astrocytomas and grade 2 oligodendrogliomas. And in the setting after surgery, they were treated with vorasidenib, and what they found is that this delayed the time to next intervention. And the key aspect of that is that it delayed when we could start radiation and chemotherapy in these patients. So what we did in the guidelines is that for both low grade oligodendrogliomas and low grade astrocytomas, we added one additional guideline statement. Our previous guideline in 2021 offered the options for observation or treatment with radiation and chemotherapy. And now in this guideline, we have options for observation, treatment with vorasidenib in those in whom we feel it is safe to defer radiation and chemotherapy, and then treatment with radiation and chemotherapy. So we've added in an additional option here. And the key message of the guideline is really on how, as clinicians, we think about using the vorasidenib and what the ideal setting for using the vorasidenib is. Brittany Harvey: Excellent. It's great to hear about this new option for patients. So then you were just talking about how we think about who to offer this IDH inhibitor to. So, Dr. Blakeley, what should clinicians know as they implement these new recommendations into practice? Dr. Jaishri Blakeley: Yes. So, first and foremost, let's go back to 2021, and a key note from those guidelines was the importance of molecular testing. And at that point, the importance of molecular testing, which in large part was focused on IDH1 or IDH2 mutations, was prognostic. We could say there's a difference in an IDH1 mutant astrocytoma and an IDH1 wild type astrocytoma, but we didn't have a specific therapeutic recommendation attached to that, like Dr. Mohile just said. And the big shift here is now we have a specific therapeutic for that population with IDH1 or IDH2 mutant glioma. So for clinicians, we hope that they've been getting molecular testing on newly diagnosed glioma already, but now there's an additional motivation to do so because it may change your treatment plan in the right circumstance. So since the publication of the phase III INDIGO study that Dr. Mohile mentioned, and the FDA approval of vorasidenib, if you meet the specified criteria in the clinical trial - which the guidelines point out is a little different than what's on the FDA label, so clinicians might want to dig into that a little bit - then there is a treatment option that is new and different than combined chemoradiation or radiation alone or observation. Brittany Harvey: I appreciate those clarifications there. So then also, Dr. Blakeley, how does this update impact patients with astrocytic or oligodendroglial tumors? Dr. Jaishri Blakeley: So first, patients also should know if they have IDH mutant gliomas. And this update only applies to people with IDH1/2 mutant glioma. Perhaps, we're not sure, it might only apply to people who are in the newly or newly-ish diagnosed category because the INDIGO study required that people were within the first five years of their surgical diagnosis and had not had other treatment. So there are a lot of people who have astrocytoma or oligodendroglioma who may or may not know their IDH1/2 status and may have already had another therapy - this update doesn't apply to them. We hope that future research will teach us about that. This update is for people who are newly diagnosed and just starting the journey to figure out the best therapy. It does say that if you do have that IDH1/2 alteration in your tumor, there is a drug therapy that is different from the drug therapies we would offer gliomas that do not have the IDH1/2 mutation. Brittany Harvey: Absolutely. I think both that emphasis on molecular testing is very important and also thinking about that study inclusion criteria and how it impacts who's eligible for this treatment. So then finally, Dr. Mohile, what are the outstanding questions about vorasidenib or other interventions for gliomas in adults? Dr. Nimish Mohile: I think the key question for clinicians is exactly who we're going to use this in. The challenges with inclusion criteria in clinical trials is they don't actually always match what we're seeing in the clinic. And I think it brings up the question of, in low grade oligodendrogliomas which we think of as very slow growing tumors, do we have the option outside of the strict inclusion criteria to use that drug in other settings? I think it brings up the question for some clinicians in some of the higher grade tumors, in the grade 3 tumors, we don't yet have data in that area and our guideline doesn't address that. But I think some will be asking what the clinical activity of vorasidenib is in that setting. There are some suggestions that the IDH inhibitors may impact seizure control, and I think that that's data that we're continuing to wait on. So I think that there's several outstanding questions there that we will have answers for hopefully in the next several years. I think the big question that we don't have an answer for and that will take a long time to know is whether the addition of vorasidenib in this setting actually improves how long people live. And given how long people with low grade oligodendrogliomas and low grade astrocytomas live today, we probably won't have an answer to that question for more than a decade. Brittany Harvey: Definitely. We'll look forward to these ongoing developments and eventually longer term data on overall survival on these agents. So, I want to thank you both so much for your work to rapidly include this information from this new trial. And thank you for your time today, Dr. Blakeley and Dr. Mohile. Dr. Jaishri Blakeley: Thank you so much. Dr. Nimish Mohile: Thank you Brittany. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/neurooncology-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

1
Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer Guideline Update 20:51

33 weeks yang lalu20:51

20:51

Dr. Ko Un "Clara" Park and Dr. Mylin Torres present the latest evidence-based changes to the SLNB in early-stage breast cancer guideline. They discuss the practice-changing trials that led to the updated recommendations and topics such as when SLNB can be omitted, when ALND is indicated, radiation and systemic treatment decisions after SLNB omission, and the role of SLNB in special circumstances. We discuss the importance of shared decision-making and other ongoing and future de-escalation trials that will expand knowledge in this space. Read the full guideline update, "Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update" at www.asco.org/breast-cancer-guidelines . TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/breast-cancer-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology , https://ascopubs.org/doi/10.1200/JCO-25-00099 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts . My name is Brittany Harvey and today I'm interviewing Dr. Ko Un "Clara" Park from Brigham and Women's Hospital, Dana-Farber Cancer Institute, and Dr. Mylin Torres from Glenn Family Breast Center at Winship Cancer Institute of Emory University, co-chairs on "Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer: ASCO Guideline Update." Thank you for being here today, Dr. Park and Dr. Torres. Dr. Mylin Torres: Thank you, it's a pleasure to be here. Brittany Harvey: And before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Torres and Dr. Park, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology , which is linked in the show notes. To start us off, Dr. Torres, what is the scope and purpose of this guideline update on the use of sentinel lymph node biopsy in early-stage breast cancer? Dr. Mylin Torres: The update includes recommendations incorporating findings from trials released since our last published guideline in 2017. It includes data from nine randomized trials comparing sentinel lymph node biopsy alone versus sentinel lymph node biopsy with a completion axillary lymph node dissection. And notably, and probably the primary reason for motivating this update, are two trials comparing sentinel lymph node biopsy with no axillary surgery, all of which were published from 2016 to 2024. We believe these latter two trials are practice changing and are important for our community to know about so that it can be implemented and essentially represent a change in treatment paradigms. Brittany Harvey: It's great to hear about these practice changing trials and how that will impact these recommendation updates. So Dr. Park, I'd like to start by reviewing the key recommendations across all of these six overarching clinical questions that the guideline addressed. So first, are there patients where sentinel lymph node biopsy can be omitted? Dr. Ko Un "Clara" Park: Yes. The key change in the current management of early-stage breast cancer is the inclusion of omission of sentinel lymph node biopsy in patients with small, less than 2 cm breast cancer and a negative finding on preoperative axillary ultrasound. The patients who are eligible for omission of sentinel lymph node biopsy according to the SOUND and INSEMA trial are patients with invasive ductal carcinoma that is size smaller than 2 cm, Nottingham grades 1 and 2, hormone receptor-positive, HER2-negative in patients intending to receive adjuvant endocrine therapy, and no suspicious lymph nodes on axillary ultrasound or if they have only one suspicious lymph node, then the biopsy of that lymph node is benign and concordant according to the axillary ultrasound findings. The patients who are eligible for sentinel lymph node biopsy omission according to the SOUND and INSEMA trials were patients who are undergoing lumpectomy followed by whole breast radiation, especially in patients who are younger than 65 years of age. For patients who are 65 years or older, they also qualify for omission of sentinel lymph node biopsy in addition to consideration for radiation therapy omission according to the PRIME II and CALGB 9343 clinical trials. And so in those patients, a more shared decision-making approach with the radiation oncologist is encouraged. Brittany Harvey: Understood. I appreciate you outlining that criteria for when sentinel lymph node biopsy can be omitted and when shared decision making is appropriate as well. So then, Dr. Torres, in those patients where sentinel lymph node biopsy is omitted, how are radiation and systemic treatment decisions impacted? Dr. Mylin Torres: Thank you for that question. I think there will be a lot of consternation brought up as far as sentinel lymph node biopsy and the value it could provide in terms of knowing whether that lymph node is involved or not. But as stated, sentinel lymph node biopsy actually can be safely omitted in patients with low risk disease and therefore the reason we state this is that in both SOUND and INSEMA trial, 85% of patients who had a preoperative axillary ultrasound that did not show any signs of a suspicious lymph node also had no lymph nodes involved at the time of sentinel node biopsy. So 85% of the time the preoperative ultrasound is correct. So given the number of patients where preoperative ultrasound predicts for no sentinel node involvement, we have stated within the guideline that radiation and systemic treatment decisions should not be altered in the select patients with low risk disease where sentinel lymph node biopsy can be omitted. Those are the patients who are postmenopausal and age 50 or older who have negative findings on preoperative ultrasound with grade 1 or 2 disease, small tumors less than or equal to 2 cm, hormone receptor-positive, HER2-negative breast cancer who undergo breast conserving therapy. Now, it's important to note in both the INSEMA and SOUND trials, the vast majority of patients received whole breast radiation. In fact, within the INSEMA trial, partial breast irradiation was not allowed. The SOUND trial did allow partial breast irradiation, but in that study, 80% of patients still received whole breast treatment. Therefore, the preponderance of data does support whole breast irradiation when you go strictly by the way the SOUND and INSEMA trials were conducted. Notably, however, most of the patients in these studies had node-negative disease and had low risk features to their primary tumors and would have been eligible for partial breast irradiation by the ASTRO Guidelines for partial breast treatment. So, given the fact that 85% of patients will have node-negative disease after a preoperative ultrasound, essentially what we're saying is that partial breast irradiation may be offered in these patients where omission of sentinel node biopsy is felt to be safe, which is in these low risk patients. Additionally, regional nodal irradiation is something that is not indicated in the vast majority of patients where omission of sentinel lymph node biopsy is prescribed and recommended, and that is because very few of these patients will actually end up having pathologic N2 disease, which is four or more positive lymph nodes. If you look at the numbers from both the INSEMA and the SOUND trial, the number of patients with pathologic N2 disease who did have their axilla surgically staged, it was less than 1% in both trials. So, in these patients, regional nodal irradiation, there would be no clear indication for that more aggressive and more extensive radiation treatment. The same principles apply to systemic therapy. As the vast majority of these patients are going to have node-negative disease with a low risk primary tumor, we know that postmenopausal women, even if they're found to have one to three positive lymph nodes, a lot of the systemic cytotoxic chemotherapy decisions are driven by genomic assay score which is taken from the primary tumor. And therefore nodal information in patients who have N1 disease may not be gained in patients where omission of sentinel lymph node biopsy is indicated in these low risk patients. 14% of patients have 1 to 3 positive lymph nodes in the SOUND trial and that number is about 15% in the INSEMA trial. Really only the clinically actionable information to be gained is if a patient has four or more lymph nodes or N2 disease in this low risk patient population. So, essentially when that occurs it's less than 1% of the time in these patients with very favorable primary tumors. And therefore we thought it was acceptable to stand by a recommendation of not altering systemic therapy or radiation recommendations based on omission of sentinel nodes because the likelihood of having four more lymph nodes is so low. Dr. Ko Un "Clara" Park: I think one thing to add is the use of CDK4/6 inhibitors to that and when we look at the NATALEE criteria for ribociclib in particular, where node-negative patients were included, the bulk majority of the patients who were actually represented in the NATALEE study were stage III disease. And for stage I disease to upstage into anatomic stage III, that patient would need to have pathologic N2 disease. And as Dr. Torres stated, the rate of having pathologic N2 disease in both SOUND and INSEMA studies were less than 1%. And therefore it would be highly unlikely that these patients would be eligible just based on tumor size and characteristics for ribociclib. So we think that it is still safe to omit sentinel lymph node biopsy and they would not miss out, if you will, on the opportunity for CDK4/6 inhibitors. Brittany Harvey: Absolutely. I appreciate you describing those recommendations and then also the nuances of the evidence that's underpinning those recommendations, I think that's important for listeners. So Dr. Park, the next clinical question addresses patients with clinically node negative early stage breast cancer who have 1 or 2 sentinel lymph node metastases and who will receive breast conserving surgery with whole breast radiation therapy. For these patients, is axillary lymph node dissection needed? Dr. Ko Un "Clara" Park: No. And this is confirmed based on the ACOSOG Z0011 study that demonstrated in patients with 1 to 3 positive sentinel lymph node biopsy when the study compared completion axillary lymph node dissection to no completion axillary lymph node dissection, there was no difference. And actually, the 10-year overall survival as reported out in 2017 and at a median follow up of 9.3 years, the overall survival again for patients treated with sentinel lymph node biopsy alone versus those who were treated with axillary lymph node dissection was no different. It was 86.3% in sentinel lymph node biopsy versus 83.6% and the p-value was non-inferior at 0.02. And so we believe that it is safe for the select patients who are early stage with 1 to 2 positive lymph nodes on sentinel lymph node biopsy, undergoing whole breast radiation therapy to omit completion of axillary lymph node dissection. Brittany Harvey: Great, I appreciate you detailing what's recommended there as well. So then, to continue our discussion of axillary lymph node dissection, Dr. Torres, for patients with nodal metastases who will undergo mastectomy, is axillary lymph node dissection indicated? Dr. Mylin Torres: It's actually not and this is confirmed by two trials, the AMAROS study as well as the SENOMAC trial. And in both studies, they compared a full lymph node dissection versus sentinel lymph node biopsy alone in patients who are found to have 1 to 2 positive lymph nodes and confirmed that there was no difference in axillary recurrence rates, overall survival or disease-free survival. What was shown is that with more aggressive surgery completion axillary lymph node dissection, there were higher rates of morbidity including lymphedema, shoulder pain and paresthesias and arm numbness, decreased functioning of the arm and so there was only downside to doing a full lymph node dissection. Importantly, in both trials, if a full lymph node dissection was not done in the arm that where sentinel lymph node biopsy was done alone, all patients were prescribed post mastectomy radiation and regional nodal treatment and therefore both studies currently support the use of post mastectomy radiation and regional nodal treatment when a full lymph node dissection is not performed in these patients who are found to have N1 disease after a sentinel node biopsy. Brittany Harvey: Thank you. And then Dr. Park, for patients with early-stage breast cancer who do not have nodal metastases, can completion axillary lymph node dissection be omitted? Dr. Ko Un "Clara" Park: Yes, and this is an unchanged recommendation from the earlier ASCO Guidelines from 2017 as well as the 2021 joint guideline with Ontario Health, wherein patients with clinically node-negative early stage breast cancer, the staging of the axilla can be performed through sentinel lymph nodal biopsy and not completion axillary lymph node dissection. Brittany Harvey: Understood. So then, to wrap us up on the clinical questions here, Dr. Park, what is recommended regarding sentinel lymph node biopsy in special circumstances in populations? Dr. Ko Un "Clara" Park: One key highlight of the special populations is the use of sentinel lymph node biopsy for evaluation of the axilla in clinically node negative multicentric tumors. While there are no randomized clinical trials evaluating specifically the role of sentinel lymph nodal biopsy in multicentric tumors, in the guideline, we highlight this as one of the safe options for staging of the axilla and also for pregnant patients, these special circumstances, it is safe to perform sentinel lymph node biopsy in pregnant patients with the use of technetium - blue dye should be avoided in this population. In particular, I want to highlight where sentinel lymph node biopsy should not be used for staging of the axilla and that is in the population with inflammatory breast cancer. There are currently no studies demonstrating that sentinel lymph node biopsy is oncologically safe or accurate in patients with inflammatory breast cancer. And so, unfortunately, in this population, even after neoadjuvant systemic therapy, if they have a great response, the current guideline recommends mastectomy with axillary lymph node dissection. Brittany Harvey: Absolutely. I appreciate your viewing both where sentinel lymph node can be offered in these special circumstances in populations and where it really should not be used. So then, Dr. Torres, you talked at the beginning about how there's been these new practice changing trials that really impacted these recommendations. So in your view, what is the importance of this guideline update and how does it impact both clinicians and patients? Dr. Mylin Torres: Thank you for that question. This update and these trials that inform the update represent a significant shift in the treatment paradigm and standard of care for breast cancer patients with early-stage breast cancer. When you think about it, it seems almost counterintuitive that physicians and patients would not want to know if a lymph node is involved with cancer or not through sentinel lymph node biopsy procedure. But what these studies show is that preoperative axillary ultrasound, 85% of the time when it's negative, will correctly predict whether a sentinel lymph node is involved with cancer or not and will also be negative. So if you have imaging that's negative, your surgery is likely going to be negative. Some people might ask, what's the harm in doing a sentinel lymph node biopsy? It's important to recognize that upwards of 10% of patients, even after sentinel lymph node biopsy will develop lymphedema, chronic arm pain, shoulder immobility and arm immobility. And these can have a profound impact on quality of life. And if there is not a significant benefit to assessing lymph nodes, particularly in someone who has a preoperative axillary ultrasound that's negative, then why put a patient at risk for these morbidities that can impact them lifelong? Ideally, the adoption of omission of sentinel lymph node biopsy will lead to more multidisciplinary discussion and collaboration in the preoperative setting especially with our diagnostic physicians, radiology to assure that these patients are getting an axillary ultrasound and determine how omission of sentinel lymph node biopsy may impact the downstream treatments after surgery, particularly radiation and systemic therapy decisions, and will be adopted in real world patients, and how clinically we can develop a workflow where together we can make the best decisions for our patients in collaboration with them through shared decision making. Brittany Harvey: Absolutely. It's great to have these evidence-based updates for clinicians and patients to review and refer back to. So then finally, Dr. Park, looking to the future, what are the outstanding questions and ongoing trials regarding sentinel lymph node biopsy in early-stage breast cancer? Dr. Ko Un "Clara" Park: I think to toggle on Dr. Torres's comment about shared decision making, the emphasis on that I think will become even more evident in the future as we incorporate different types of de-escalation clinical studies. In particular, because as you saw in the SOUND and INSEMA studies, when we de-escalate one modality of the multimodality therapy, i.e., surgery, the other modalities such as radiation therapy and systemic therapy were "controlled" where we were not de-escalating multiple different modalities. However, as the audience may be familiar with, there are other types of de-escalation studies in particular radiation therapy, partial breast irradiation or omission of radiation therapy, and in those studies, the surgery is now controlled where oftentimes the patients are undergoing surgical axillary staging. And conversely when we're looking at endocrine therapy versus radiation therapy clinical trials, in those studies also the majority of the patients are undergoing surgical axillary staging. And so now as those studies demonstrate the oncologic safety of omission of a particular therapy, we will be in a position of more balancing of the data of trying to select which patients are the safe patients for omission of certain types of modality, and how do we balance whether it's surgery, radiation therapy, systemic therapy, endocrine therapy. And that's where as Dr. Torres stated, the shared decision making will become critically important. I'm a surgeon and so as a surgeon, I get to see the patients oftentimes first, especially when they have early-stage breast cancer. And so I could I guess be "selfish" and just do whatever I think is correct. But whatever the surgeon does, the decision does have consequences in the downstream decision making. And so the field really needs to, as Dr. Torres stated earlier, rethink the workflow of how early-stage breast cancer patients are brought forth and managed as a multidisciplinary team. I also think in future studies the expansion of the data to larger tumors, T3, in particular,reater than 5 cm and also how do we incorporate omission in that population will become more evident as we learn more about the oncologic safety of omitting sentinel lymph node biopsy. Dr. Mylin Torres: In addition, there are other outstanding ongoing clinical trials that are accruing patients right now. They include the BOOG 2013-08 study, SOAPET, NAUTILUS and the VENUS trials, all looking at patients with clinical T1, T2N0 disease and whether omission of sentinel lymph node biopsy is safe with various endpoints including regional recurrence, invasive disease-free survival and distant disease-free survival. I expect in addition to these studies there will be more studies ongoing even looking at the omission of sentinel lymph node biopsy in the post-neoadjuvant chemotherapy setting. And as our imaging improves in the future, there will be more studies improving other imaging modalities, probably in addition to axillary ultrasound in an attempt to accurately characterize whether lymph nodes within axilla contain cancer or not, and in that context whether omission of sentinel lymph node biopsy even in patients with larger tumors post-neoadjuvant chemotherapy may be done safely and could eventually become another shift in our treatment paradigm. Brittany Harvey: Yes. The shared decision making is key as we think about these updates to improve quality of life and we'll await data from these ongoing trials to inform future updates to this guideline. So I want to thank you both so much for your extensive work to update this guideline and thank you for your time today. Dr. Park and Dr. Torres. Dr. Mylin Torres: Thank you. Dr. Ko Un "Clara" Park: Thank you. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/breast-cancer-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

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Fertility Preservation in People with Cancer Guideline Update 32:09

36 weeks yang lalu32:09

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Dr. Irene Su and Dr. Alison Loren present the latest evidence-based recommendations on fertility preservation for people with cancer. They discuss established, emerging, and investigational methods of fertility preservation for adults and children, and the role of clinicians including discussing the risk of infertility with all patients. Dr. Su and Dr. Loren also touch on other important aspects of fertility preservation, including the logistics of referral to reproductive specialists, navigating health insurance, and costs. They also discuss ongoing research and future areas to explore, including risk stratification, implementing screening, referral, and navigation processes in lower resource settings, fertility measurements, and health care policy impacts. Read the full guideline update, " Fertility Preservation in People with Cancer: ASCO Guideline Update " at www.asco.org/survivorship-guidelines ." TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/survivorship-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology , https://ascopubs.org/doi/10.1200/JCO-24-02782 In this guideline, the terms "male" and "female" were defined based on biological sex, specifically focusing on reproductive anatomy at birth. "Male" refers to individuals born with testes, while "female" refers to those born with ovaries. The guideline, and this podcast episode, we will refer to individuals as "males" or "females" based on this definition. Brittany Harvey Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one at asco.org/podcasts . My name is Brittany Harvey and today I'm interviewing Dr. Irene Su from the University of California, San Diego, and Dr. Alison Loren from the University of Pennsylvania, co-chairs on "Fertility Preservation in People With Cancer: ASCO Guideline Update." Thank you for being here today, Dr. Su and Dr. Loren. Dr. Irene Su: Thanks for having us. Dr. Alison Loren: Thanks for having us. Brittany Harvey: Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Su and Dr. Loren, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology , which is linked in the show notes. So then, to jump into the content here, Dr. Loren, this is an update of a previous ASCO guideline. So what prompted this update to the 2018 guideline on fertility preservation? And what is the scope of this particular update? Dr. Alison Loren: Yeah, thanks, Brittany. So, yeah, a couple of things, actually. I would say the biggest motivation was the recognition that the field was really moving forward in several different directions. And we felt that the previous guidelines really hadn't adequately covered the need for ongoing reproductive health care in survivorship, including the fact that fertility preservation methods can be engaged in even after treatment is finished. And then also recognizing that there is increasing data supporting various novel forms of fertility preservation in both male and female patients. And we wanted to be able to educate the community about the wide array of options that are available to people with cancer, because it really has changed quite a bit even in the last six years. And then lastly, as I'm sure this audience, and you definitely know, ASCO tries to update the guidelines periodically to make sure that they're current. So it sort of is due anyhow, but I would say motivated largely by those changes in the field. Brittany Harvey: Great. I appreciate that background information. So then I'd like to dive a little bit more into those updates that you discussed. So, Dr. Su, I'd like to review the key recommendations across the main topics of this guideline. So starting with what are the recommendations regarding discussing the risk of infertility with patients undergoing cancer treatment? Dr. Irene Su: Thanks, Brittany. So for every child, adolescent, and adult of reproductive age who's been diagnosed with cancer, the recommendation remains that healthcare clinicians should discuss this possibility of infertility as early as possible before treatment starts, because that allows us, as reproductive endocrinologists and fertility specialists, to preserve the full range of options for fertility preservation for these young people. Where it's possible, I think risk stratification should be a part of the clinical infertility risk counseling and then the decision making. And then for patients and families who have an expressed interest in fertility preservation, and for those who are uncertain, the recommendation is to refer these individuals to reproductive specialists. And it turns out this is because fertility preservation treatments are medically effective for improving post-treatment fertility and counseling can ultimately reduce stress and improve quality of life, even for those who don't undergo fertility preservation. And as Dr. Loren said, a change in the guideline is specifically about continuing these discussions post-treatment yearly or when cancer treatments change because that changes their infertility risk or when pregnancy is being considered. Brittany Harvey: Absolutely. Discussing that risk of infertility at the beginning, before any treatment is initiated, and when treatment changes, is key. So then talking about the options for patients, Dr. Loren, what are the recommended fertility preservation options for males? Dr. Alison Loren: There has been a little bit of an evolution in options for male patients. The standard of care option which is always recommended is cryopreservation of sperm, or otherwise known as sperm banking. And this is something that should be offered ideally prior to initiating cancer directed therapy. The guideline does reflect the fact that we're starting to understand in a little bit more depth the impact of cancer-directed treatments on the health and quantity of sperm. And so trying to understand when, if ever, it's appropriate to collect sperm after initiation of treatment, but before completion of treatment remains an area of active research. But the current understanding of the data and the evidence is that sperm banking should be offered prior to initiating cancer-directed therapy. And all healthcare clinicians should feel empowered to discuss this option with all pubertal and post-pubertal male patients prior to receiving their treatment. We do offer a little bit more information about the ideal circumstances around sperm banking, including a minimum of three ejaculates of sufficient quality, if possible, but that any collections are better than no collections. We also talk about the fact that there is a relatively new procedure known as testicular sperm extraction, which can be offered to pubertal and post-pubertal males who can't produce a semen sample before cancer treatment begins. There remains no evidence for hormonal protection of testicular function - that has been a long-standing statement of fact and that remains the case. And then we also begin to address some of the potential risk of genetic damage in sperm that are collected soon after initiation of cancer-directed therapy. We are starting to understand that there is a degradation in the number and DNA integrity of sperm that can occur even after a single treatment. And so, really highlighting the fact that collecting samples, again, to Dr. Su's point, as early as possible and as many as possible to try to optimize biological parenthood after treatment. Brittany Harvey: Yes. Thank you for reviewing those options and what is both recommended and not recommended in this scenario. So then, following those recommendations, Dr. Su, what are the recommended fertility preservation options for female patients? Dr. Irene Su: There are a number of established and effective methods for fertility preservation for people with ovaries, and this includes freezing embryos, freezing oocytes, freezing ovarian tissue. For some patients, it may be appropriate to do ovarian transposition, which is to surgically move ovaries out of the field of radiation in a conservative gynecologic surgery, for example, preserving ovaries or preserving the uterus in people with gynecologic cancers. We do recommend that the choice between embryo and oocyte cryopreservation should be guided by patient preference and clinical considerations, their individual circumstances, including future flexibility, the success rates of embryo versus egg freezing that we detail more in the guideline, and legal considerations. And what is new in this guideline, as Dr. Loren alluded to earlier, is consideration of post-treatment fertility preservation for oocyte and embryo freezing. And this is going to be because, for some females, there's going to be a shortened but residual window of ovarian function that may not match when they are in their life ready to complete their families. And so for those individuals, there may be an indication to consider post-treatment fertility preservation. We clarify that gonadotropin releasing hormone agonists, GNRH agonists, while they shouldn't be used in the place of established fertility preservation methods, e.g., oocyte and embryo freezing, they can definitely be offered as an adjunct to females with breast cancer. Beyond breast cancer, we don't really understand the benefits and risks of GNRH agonists and feel that clinical trials in this area are highly encouraged. And also, that for patients who have oncologic emergencies that require urgent chemotherapy, these agonists can be offered because they can provide additional benefits like menstrual suppression. What's emerging is in vitro maturation of oocytes. It's feasible in specialized labs. It may take a little bit shorter time to retrieve these oocytes. There are cases of live births following IVM, in vitro maturation, that have been reported. But these processes remain inefficient compared to standard controlled ovarian stimulation. And therefore, it's really being treated as an emerging method. Finally, uterine transposition. It's experimental, but it's a novel technique for us. It's really moving the uterus out of the field of radiation surgically. We recommend that this is done under research protocols. So taken together, there are improvements in fertility preservation technology, and consideration of which of any of these methods really depends on tailoring to what is that patient's risk, what is the time that they have, what is feasible for them, and what is the effectiveness comparatively among these methods for them. Brittany Harvey: I appreciate you reviewing those recommendations and considerations of patient preferences, the clarification on GNRH agonists, and then those emerging and experimental methods as well. So then the next category of recommendations, Dr. Loren, what are the recommended fertility preservation options for children? Dr. Alison Loren: Thanks, Brittany. This remains a very challenging area. Certainly for older children and adolescents who have begun to initiate puberty changes, we support proceeding with previously outlined standard methods of either sperm or oocyte collection and cryopreservation. For younger children who are felt to be at substantial risk for harm to fertility, the really only options available to them are gonadal tissue cryopreservation, so ovarian tissue or testicular tissue cryopreservation. As Dr. Su mentioned, the ovarian tissue cryopreservation methods are quite effective and well established. There's less data in children, but we know that in adults and older adolescents that this is an effective method. Testicular cryopreservation remains experimental, and we suggest that if it is performed, that strong consideration should be given to doing this as an investigational research protocol. However, because these are the only options available to children, we understand there may be reasons why there might need to be some flexibility around this in the proper setting of informed consent and ascent when appropriate for children. Brittany Harvey: Absolutely. And so we've discussed a lot of recommendations on fertility preservation options. So, Dr. Loren, what is recommended regarding the role of clinicians in advising people about these fertility preservation options? Dr. Alison Loren: Yeah, this is a really important question, Brittany, and I think that we really hope to empower the entire oncology clinical team to bring these issues to the forefront for patients. We know from qualitative studies that oncology providers sometimes feel uncomfortable bringing these issues up because they feel inexpert in dealing with them or because it's so overwhelming. Obviously, these are usually younger patients who are not expecting a cancer diagnosis, and there can be quite a lot of distress, understandably, around the diagnosis itself and the treatment plan, and it can be sometimes overwhelming to also bring up fertility as a potential risk of therapy. We are seeing that as patients are becoming more familiar and comfortable kind of speaking up, I think, social media and lots of sort of online communities have raised this issue, that we're seeing that young people with cancer do spontaneously bring this up in their visits, which we really appreciate and encourage. But I think sometimes clinicians feel it's sometimes described as a dual crisis of both the cancer diagnosis and a risk to future fertility and it can be a really challenging conversation to initiate. I feel, and we hope that the guidelines convey, that the whole point is just to bring it up. We do not expect an oncology clinician of any kind, including social workers, nurses, to be able to outline all of the very complex options that are articulated in this guideline. And in fact, the reason that the co-chairs include myself, a hematologist oncologist, and Dr. Su, who's a reproductive specialist, is because we understand that the complex reproductive options for our patients with cancer require expert conversations. So we do not expect the oncology team to go into all the guideline options with their patients. We really just want to empower everyone on the team to bring up the issue so that we can then get them the care that they need from our colleagues in reproductive endocrinology so that they can be fully apprised of all of their options with enough time before initiation of treatment to be able to embark on whichever therapies they feel are most suited to their family planning wishes. Brittany Harvey: Absolutely. And then jumping off of that, as a reproductive endocrinologist, Dr. Su, what do you think clinicians should know as they implement these updated recommendations? Dr. Irene Su: I wholly echo what Dr. Loren has said about- this is a team effort and it's been really fun to work as a team of various specialties on this guideline, so we hope that the guideline really reflects all of the partnerships that have occurred. I think that what clinicians should know is it may be well worth spending some time in identifying a pathway for our patients. So that starts off with the oncology team. How are we going to screen? How are we going to screen with fidelity? And then from the time of screening, really anybody who has an interest or potentially is unsure about their future fertility needs, who are the reproductive specialists, male and female, that you are in the community with to refer to? What is that referral process going to be like? Is it emails? Is it a phone? Is it a best practice advisory in your electronic health record system? From our standpoint as fertility specialists, we need to spend some time implementing in this system a way to receive these referrals urgently and also be able to support insurance navigation. Because actually, what is really exciting in this field is for the purpose of equitable access, there is increasing insurance coverage, whether it is because employers feel that this is the right thing to do to offer, or 17 states and the District of Columbia also have state mandates requiring fertility preservation coverage by many insurances, as well as, for example, federal employees and active military members. So more than ever, there is a decreased cost barrier for patients and still early days, so navigating health insurance is a little bit challenging. And that is the role, in part, of navigators and fertility clinic teams to help support these patients to do that. Dr. Alison Loren: Forming these relationships and reinforcing them so early and often is really key. Because although these patients come up with some infrequency, when they occur, they're really emergencies and we want to make sure that there's a well-established path for these patients to get from their oncology clinicians to the reproductive specialists. And as Dr. Su said, whatever works best for your system - there's a lot of different ways that people have tackled these challenging referrals - but it is really important to have an expedited path and for the receiving reproductive specialist office to understand that these are urgent patients that need to be expedited and that the oncology clinician's responsibility is to make sure that that's communicated appropriately. Brittany Harvey: Definitely. Thinking in advance about those logistics of referral and navigating health insurance and cost is key to making sure that patients receive the care that they want and that they'd like to discuss with clinicians. So then, Dr. Loren, you touched on this a little bit earlier in talking about the dual crisis, but how does this guideline impact people diagnosed with cancer? Dr. Alison Loren: Well, what we're hoping is that this is sort of a refresher. I think that many or hopefully most or all oncology clinicians are aware that this is a potential concern. And so part of our hope is that, as this guideline rolls out, it'll sort of bring to the top of people's memories and action items that this is an important part of oncology care is the reproductive health care of our patients. And it's a critical component of survivorship care as well. We want to remind people that the field continues to advance and progress. In oncology, we're very aware of oncologic progress, but we may not be so aware of reproductive healthcare progress. And so letting people know, "Hey, there's all these new cool things we can do for people that open up options, even in situations where we might have thought there were no options before." It's a reminder to refer, because we're not going to be able to keep up with all the advances in the field. But Dr. Su and her colleagues will be able to know what might be an option for patients. I want to highlight that communication piece again because our reproductive colleagues need to know what treatments are going to be given, what the urgency is, what the risks are. And so part of our responsibility as part of the team is to make sure that it's clear to both our patients and our reproductive specialist colleagues what the risks are. And Dr. Su mentioned this earlier, but one really important open question is risk stratification. We know that not all cancer treatments are created equal. There are some treatments, such as high dose alkylating agents, such as cyclophosphamide or busulfan, or high doses of radiation directly to the gonadal tissue, that are extremely high risk for causing permanent gonadal harm very immediately after exposure. And there are other therapies, particularly emerging or novel therapies, that we really just have no idea what the reproductive impact will be. And in particular, as patients are living longer, which is wonderful for our patients, how do we integrate reproductive care and family building into the management of perhaps a younger person who's on some chronic maintenance therapies, some of which we know can harm either the developing fetus or reproductive health, and some of which we really don't know at all. And so there's a very large open question around emerging therapies and how to counsel our patients. And so we hope that this guideline will also raise to the forefront the importance of addressing these questions moving forward and helping our patients to understand that we don't necessarily have all the answers either, which we hope will enrich the discussion and really have it be a good example of shared decision making between the clinical teams and the patient, so that ultimately the patients are able to make decisions that make the most sense for them and reduce the potential for decision regret in the future. Dr. Su, I know you have spent a lot of time thinking about this. Dr. Irene Su: Yeah. I really echo this notion that not all cancer treatments are going to be toxic to future reproductive function. And as clinicians, I and colleagues know that patients want to know as much when there is no effect on their fertility, because that feels reassuring in that that prevents them from having to go through the many hoops that sometimes it can be to undergo fertility preservation, as it is to know high risk, as it is to know we don't know. This is key and central, and we need more data. So, for example, we often chat about, wouldn't it be great if from the time of preclinical drug development all the way to clinical trials, that reproductive health in terms of ovarian function, testicular function, fertility potential, is measured regularly so that we are not having to look back 30, 40, 50 years later to understand what happened. And so this is one of our key research questions that we hope the field takes note of going forward. Dr. Alison Loren: This is an important point. We focus greatly, as we should, on potential harms to fertility, making sure that there's access to all the reproductive options for young people with cancer. But to Dr. Su's point, not all therapies are created equal, and there are some therapies that are somewhat lower risk or even much lower risk, including, I'm a blood cancer specialist and so certainly in the patients that I take care of, the treatments related to AML, ALL, and some lymphomas are actually fairly low risk, which is why the post-treatment fertility preservation options are so important. And particularly for patients who potentially present acutely ill with acute leukemia do not have the time or the ability to engage in fertility preservation because of their medical circumstances, it's important to have that conversation. I want to emphasize to oncology clinicians that even if you know medically that this patient is unable to undergo fertility preservation techniques at the time of diagnosis of their cancer, that it's still appropriate to talk about it and to say, "We're going to keep talking about this, this is something that we're going to raise again once you're through this initial therapy. I'm not forgetting about this. It may not be something we can engage in now, but it's a future conversation that's important in your ongoing care." And then to think about pursuing options when possible, particularly for patients who may require a bone marrow transplant in their future, either due to higher risk disease at presentation or in the event of a relapse, we know that generally bone marrow transplants, because of the high intensity conditioning that they require for most patients who are young, that permanent gonadal insufficiency will be a fixture. And so there can be a window of time in between initial therapy and transplant where a referral might be appropriate. So my public service announcement is that it's never the wrong time to refer to a reproductive specialist. And sometimes people make assumptions about chemotherapy that, "Oh, they've already been treated, so there's nothing we can do," and I want to make sure that people know that that's not true and that it's always appropriate to explore options. Dr. Irene Su: I think we talk a lot about how important screening and referral is and I can imagine that it's hard to actually know how to implement that. One of our other research questions to look out for is that we see a lot of tertiary care centers that have put together big teams, big resources, and that's not always feasible to scale out to all kinds of settings. And so what's emerging is: What are the key processes that have to happen and how can we adapt this screening, referral, financial navigation process from larger centers to smaller centers to less resource settings. So I guess my public service announcement is there's research in this area, there's focus in this area, so keep an eye out because there will be hopefully better tools to be able to fit in different types of settings. And more research is actually needed to be able to trial these different screening, referral, navigation processes in lower resource settings as well. Brittany Harvey: Absolutely. It's important to think about the research questions on how to improve both the delivery of fertility preservation options and the discussion of it, and it's important to recognize, as you mentioned, the different fertility risks of different cancer directed treatment options and the importance to have the conversations around this. So then just to expand on this notion a little bit, Dr. Su, we've touched on the research needed here in terms of discussing fertility options with patients and referring and then also in some of the experimental and emerging treatment options. So, what are the other outstanding research questions regarding fertility preservation for people with cancer? Dr. Irene Su: A couple others I'd like to add and then have Dr. Loren chime in in case I missed anything in all of our discussions, there's so many wants. So head to head comparisons of which method is best for which patient and what the long term outcomes are: How many kiddos? Do we complete family building? That is still missing. Being able to invest in novel methods from - there's fertoprotective agents that are being tested, potentially spermatogonial stem cell transplant. These are closer to clinical trials to really early research on ovarian, testicular, uterine biology. This is needed in order to inform downstream interventions. One of the questions that is unanswered is: After treatment starts, when is it safe to retrieve oocytes? And so this is a question because, for example, for our leukemia patients who are in the middle of treatment, when is it safe to retrieve eggs? And we don't know. And then post-treatment, for people who have a reduced window, when do you optimally have the most number of eggs or embryos that you can cryopreserve? That's unknown. But I think the question around once treatment has started, is recent exposure of anti-cancer treatments somehow mutagenic or somehow toxic to the oocytes with regard to long term offspring health? That is unanswered. I'm going to scope out a little bit and maybe policy nerd this a little bit. It's been very exciting to see advocacy, advocacy from our patients, from our clinicians on trying to improve health care policy. Like how can we use mandates to improve this delivery? But we actually don't know because actually the mandates from states that require health insurance coverage for fertility preservation, they vary. And so actually what are the key ingredients and policies that will ultimately get the most patients to the care they need? That is in question and would be really interesting. And so what is a part of this guideline which is not often seen in clinical guidelines, is a call for what we think are best practices for health insurance plans to help patients be able to access. And so this means that we recommend being specific and comprehensive in the coverage of these established fertility preservation services that have been recommended. And this means, for example, an egg freezing covering the whole process from consultation to office visits, to ultrasounds and laboratories, to medicines, to the retrieval, and then to long term storage. Because particularly for the youngest of our patients, these gametes could be frozen for a number of years and may not always be so affordable without health insurance coverage. We think that fertility preservation benefits really should be at parity, that you should not be having more cost sharing on the patient compared to other medical services that are covered. This is an inequity and where possible we should eliminate prior authorization because that timing is so short between diagnosis and needing to start anti-cancer treatment. And so prior authorization having to go through multiple layers of health insurance is really a key barrier because we all know that health insurance literacy is limited for all of us. And so whatever we can do to support our patient for the intent of these benefits would be recommended. Dr. Alison Loren: That was so well said, Dr. Su. I'll take the oncology perspective and say that from our side, really being able to understand the risks of infertility and understanding better measurements of fertility capacity, understanding where our patients are - every patient is different. These conversations are very different for a 37-year-old than they are for a 17-year-old. And so what we haven't really talked about is the fact that certainly at least female patients, as they age, their reproductive potential declines naturally. And so their infertility trajectory may be accelerated, they may have a shorter timeline or have less reserve than younger patients. And so being able to tailor our risk discussions not just based on the specific treatments, but on the reproductive age of the patient sitting in front of us and really being able to tailor those to very personalized risks would be really helpful. Because, as Dr. Su mentioned, and I think, as many people know, undergoing fertility preservation techniques can be really arduous. Even if they're covered and paid for, and all of those logistics are easy, which they seldom are, the physical drain of having to do injections, go for labs, all of the parts of those therapies can be really difficult for patients. And so being able to really understand who needs to have these interventions and who could pass, and understanding what the risks are, as I mentioned earlier, for these novel and emerging therapies would be really helpful. Another really important aspect of future research questions is we would like to encourage all clinicians, both reproductive specialists and oncology clinicians, and also our young people with cancer, to participate in clinical studies pertaining to fertility measurements and preservation. We also exhort our industry colleagues to consider including important reproductive endpoints, including biomarkers of ovarian and testicular reserve, if possible, in clinical trials. It will enhance our ability to provide counseling and support for these therapies in the future to be able to understand what the true impact of infertility, family building and health of offspring to be able to include these data in prospective databases and trials. Brittany Harvey: Definitely. And I want to thank you both for raising those really important points. So we'll look forward to this ongoing research and optimizing policies for covering fertility preservation benefits for all patients with cancer. I want to thank you both so much for your work to update this critical guideline and talk about these important needs of people with cancer. And thank you for your time today, Dr. Su and Dr. Loren. Dr. Alison Loren: Thanks so much for having us. Dr. Irene Su: You're welcome. This was really fun. Dr. Alison Loren: It was fun. And I just will add that the team at ASCO is amazing and really made this a pleasure. Dr. Irene Su: I couldn't agree more. And from the point of being a fertility specialist, being invited to be a part of this with ASCO and with all of our colleagues, it's been really amazing. And so thanks for allowing us to contribute. Brittany Harvey: Definitely. And a big thanks to the entire panel as well. And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/survivorship-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

1
Opioid Conversion in Adults with Cancer: MASCC-ASCO-AAHPM-HPNA-NICSO Guideline 20:19

38 weeks yang lalu20:19

20:19

Dr. Mellar Davis discusses the joint guideline from MASCC, ASCO, AAHPM, HPNA, and NICSO on opioid conversion in adults with cancer. He reviews the limited evidence, and the formal consensus process used to develop the guideline. He shares the key recommendations on pre-conversion assessment, how opioid conversion should be conducted, including opioid conversion ratios, and post-conversion assessment. We touch on gaps and questions in the field and the impact of these new recommendations. Read the full guideline, " Opioid Conversion in Adults with Cancer: MASCC-ASCO-AAHPM-HPNA-NICSO Guideline " at www.asco.org/supportive-care-guidelines . TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/supportive-care-guidelines . Read the full text of the guideline in the Supportive Care in Cancer, https://link.springer.com/article/10.1007/s00520-025-09286-z Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts . My name is Brittany Harvey and today I'm interviewing Dr. Mellar Davis from Geisinger Medical Center, lead author on "Opioid Conversion in Adults with Cancer: Multinational Association of Supportive Care and Cancer, American Society of Clinical Oncology, American Academy of Hospice and Palliative Medicine, Hospice and Palliative Nurses Association, Network Italiano Cure di Supporto and Oncologia Guideline." Thank you for being here today, Dr. Davis. Dr. Mellar Davis: Thank you. I'm glad to be here. Brittany Harvey Before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Davis, who has joined us here today, are available online with the publication of the guideline , which is linked in our show notes. So then, to dive into the content here, Dr. Davis, can you provide an overview of both the scope and purpose of this guideline on opioid conversion in people with cancer? Dr. Mellar Davis: This is an important topic in management of cancer pain and this topic came up as a result of a survey that MASCC had done, which involved 370 physicians in 53 countries. They were queried about how they change or convert one opioid to another, which is a common practice, and we found that there was quite a divergence in opioid conversion ratios. To step back a little bit, about two thirds of patients with advanced cancer have moderate to severe pain and most of the time they're managed by opioids. But about 20% or 40% require a switch either because they have an adverse reaction to it or they don't respond to it, or the combination of both. Rarely, it may be that they need a route change, perhaps because they have nausea or vomiting. So, the opioid conversion works basically because of the complexity of the new opioid receptor which has at least four exons to it as a result of that non-cross tolerance between opioids. As a result of the survey, we convened a group of specialists, 14 international specialists, to look to see if we could develop an international guideline. And we did a systematic review which involved viewing 21,000 abstracts and we came up with 140 randomized trials and 68 non-randomized trials. And after reviewing the data, we found that the data was really not strong enough to provide a guideline. As a result, ASCO, MASCC, the AAHPM, the HPNA and the Italian Group formed a supportive network that allowed us then to do a Delphi guideline based upon ASCO modified criteria for doing Delphi guidelines. And so we then involved 27 additional international experts informing the guideline to it. And this guideline is then the result of the Delphi process. It consists basically of a pre-conversion ratio recommendations, conversion ratios, which is actually a major contribution of this guideline, and then what to do after converting someone to another opioid. Our target audience was not only oncologists, but also we wanted to target nurses, pharmacists, hospitalists, primary care physicians, patients and caregivers. Brittany Harvey: I appreciate that background information, particularly on the evidence that is underpinning this and the lack of quality of evidence there, which really transformed this into a formal consensus guideline. We're glad to have all of these organizations coming together to collaborate on this guideline. So then next I'd like to review the key recommendations. So starting with, what is recommended for pre-conversion assessment? Dr. Mellar Davis: In regards to pre-conversion, physicians and clinicians need to be aware of pain phenotypes. That is, there are pains that are more opioid refractory than others, such as neuropathic pain, hence, they may be more resistant to the opioid that you're converting to. One needs to be aware of the fact that patients may not be compliant, they're either afraid of opioids not taking what was prescribed, so it's important to query patients about whether they are taking their opioid as prescribed. Occasionally, there are patients who will divert their medication for various reasons. Pain may be poorly controlled also because of dosing strategies that are poorly conceived, in other words, giving only 'as needed' opioids for continuous cancer pain. And there are rare circumstances where an opioid actually induces pain and simply reducing the opioid actually may improve the pain. The other issue may be cancer progression. So that poorly controlled pain or rapidly increasing pain may actually be a result of progressive cancer and changing treatment obviously will be important. And you need to assess the pain severity, the quality of the pain, the radiating localizing effects, which does require not only a physical exam but also radiographic examinations. But the other thing that's very important in opioid conversions are pain scales with function. A significant number of patients don't quite understand a numerical scale which we commonly use: 0 to 10, with 10 being severe pain and 0 being no pain. They may in fact focus more on function rather than on pain severity or pain interference with daily activities or roles. Sometimes patients will say, "Oh, my pain is manageable," or "It's tolerable," rather than using a numerical scale. Choices of opioids may be based on cost, drug-drug interactions, organ function, personal history or substance use disorder so that one will want to choose an opioid that's safe when converting from one to another. And obviously social support and having caregivers present and understanding the strategy in managing pain will be important. Brittany Harvey: Thank you, Dr. Davis, for reviewing those pre-conversion assessment considerations and particularly the challenges around some of those. So, following this pre-conversion assessment, what are the recommendations on how opioid conversion should be conducted? Dr. Mellar Davis: Opioid conversions are basically the safe dose. People have used the term 'equianalgesia', but the panel and the consensus group felt that that would be inappropriate. So a conversion ratio is the dose at which the majority of patients will not experience withdrawal or adverse effect. It would be the safe dose. Thereafter, the dose will need to be adjusted. So, in converting, that's only the first step in managing pain, the doses need to be adjusted to the individual thereafter. There are a significant number of conversions that are done indirectly, that is that there has not been a study that has looked at a direct conversion from one opioid to another in which one needs to convert through another opioid. We call that a 'morphine equivalent daily dose'. So, most of the time a third opioid is used in the conversion. It allows you then to convert when there hasn't been a direct study that has looked at conversion between those two opioids, but it is less accurate and so one has to be a little bit more careful when using morphine daily equivalents. We found, and I think this is the major advantage to the guideline, is that commonly used opioids - oxycodone, morphine, hydromorphone - we did establish conversion ratios to which we found in the MASCC guideline they were widely divergent and hope that actually, internationally, they will be adopted. We also found some conversion ratios for second-line opioids. However, we felt also that an opioid like methadone, which has a unique pharmacology, should be left to experts and that experts should know at least several ways of converting from morphine usually to methadone. There is what appears to be a dose-related increased potency of methadone relative to morphine, which makes it more difficult, particularly at higher doses, to have an accurate conversion ratio. Most patients will have transient flares of pain. We came up with two suggestions. One is using a 10 or 15% of the around-the-clock dose for the breakthrough dose, but we also realized that there was a poor correlation between the around-the-clock dose and the dose used for transient flares of pain. And so the breakthrough dose really needs to be adjusted to the individual responses. There was also a mention of buprenorphine. One of the unique things about buprenorphine is that if you go from high doses of a drug like morphine to buprenorphine in a stop-start dosing strategy, you can precipitate withdrawal. And so one has to be careful and have some experience in using buprenorphine, which can be an effective analgesic. Brittany Harvey: Yes, I think that the conversion ratios that you mentioned that are in Table 3 in the full guideline are a really useful tool for clinicians in practice. And I appreciate the time that the panel and the additional consensus panel went through to develop these. I think it's also really key what you mentioned about these not being equianalgesic doses and the difficulties in some of these conversions and when people need to really look to specialists in the field. So then, following opioid conversion, what assessments are recommended post-conversion? Dr. Mellar Davis: Post-conversion, probably the cardinal recommendation is close observation for response and for toxicity. And I think that probably summarizes the important parts of post-conversion follow up. So assessment should be done 24-48 hours after conversion and patients followed closely. Assessment scales should include patient personalized goals. Now, it used to be in the past that we had this hard stop about a response being below 4 on a 0 to 10 scale, but each patient has their own personal goals. So they gauge the pain severity and their function based upon response. So a patient may function very well at "a severity of 5" and feel that that is their personal goal. So I think the other thing is to make sure that your assessment is just not rote, but it's based upon what patients really want to achieve with the opioid conversion. The average number of doses per day should be assessed in the around-the-clock dose so those should be followed closely. Adverse effects can occur and sometimes can be subtle. In other words, a mild withdrawal may produce fatigue, irritability, insomnia and depression. And clinicians may not pick up on the fact that they may be actually a bit under what patients have or they're experiencing withdrawal syndrome. It's important to look for other symptoms which may be subtle but indicating, for instance, neurotoxicity from an opioid. For instance, visual hallucinations may not be volunteered by patients. They may transiently see things but either don't associate with the opioid or are afraid to mention them. So I think it's important to directly query them, for instance, about visual hallucinations or about nightmares at night. Nausea can occur. It may be temporary, mild, and doesn't necessarily mean that one needs to stop the second opioid. It may actually resolve in several days and can be treated symptomatically. Pruritus can occur and can be significant. So close observation for the purposes of close adjustments are also necessary. As we mentioned, you want to start them on an around-the-clock of breakthrough dose, but then assess to see what their response is and if it's suboptimal then you'll need to adjust the doses based both upon the around-the-clock and the breakthrough dose or the dose that's used for breakthrough pain. Also looking at how patients are functioning, because remember that patients frequently look at pain in terms of function or interference with their roles during the day. So, if patients are able to do more things, that may, in fact, be the goal. Brittany Harvey: Thank you for reviewing all of these recommendations across pre-conversion assessment, how opioid conversion should be conducted, including conversion ratios, and what assessments are recommended after opioid conversion. I think it's really important to be watching for these adverse events and assessing for response and keeping in mind patient goals. So, along those lines, how will these guideline recommendations impact both clinicians and people with cancer? And what are the outstanding questions we're thinking about regarding opioid conversion? Dr. Mellar Davis: I think it's important to have a basic knowledge of opioid pharmacology. There's, for instance, drugs that are safer in liver disease, such as morphine, hydromorphone, which are glucuronidated. And there are opioids that are safer in renal failure, such as methadone and buprenorphine, which aren't dependent upon renal clearance. I think knowing drug-drug interactions are important to know. And sometimes, for instance, there may be multiple prescribers for a patient. The family physician's prescribing a certain medication and the oncologist is another, so being aware of what patients are on, and particularly over-the-counter medications which may influence opioid pharmacokinetics. So complementary medications, for instance, being aware of cannabis, if patients are using cannabis or other things, I think, are important in this. There are large gaps and questions and that's the last part of the guideline that we approach or that we mentioned that I think are important to know. And one is there may be ethnic differences in population in regards to clearance or cytochrome frequencies within communities or countries, which may actually alter the conversion ratios. This has not been explored to a great extent. There's opioid stigmata. So we are in the middle of an opioid crisis and so people have a great fear of addiction and they may not take an opioid for that reason, or they may have a relative who's been addicted or had a poor experience. And this may be particularly true for methadone and buprenorphine, which are excellent analgesics and are increasingly being used but may in fact have the stigmata. There are health inequalities that occur related to minority groups that may in fact not get the full benefit of opioid conversions due to access to opioids or to medical care. Age, for instance, will cause perhaps differences in responses to opioids and may in fact affect conversion ratios. And this may be particularly true for methadone, which we have not really explored to a great extent. And finally, the disease itself may influence the clearance or absorption of an opioid. So for a sick patient, the opioid conversion ratio may be distinctly different than in a healthy individual. This is particularly seen with transdermal fentanyl, which is less well absorbed in a cachectic patient, but once given IV or intravenously has a much longer half life due to alterations in the cytochrome that clears it. And so conversion ratios have frequently been reported in relatively healthy individuals with good organ function and not that frequently in older patient populations. So just remember that the conversion ratios may be different in those particular populations. Brittany Harvey: Yes. So I think a lot of these are very important things to consider and that managing cancer pain is key to quality of life for a lot of patients and it's important to consider these patient factors while offering opioid conversion. I want to thank you so much for your work to review the existing literature here, develop these consensus-based recommendations and thank you for your time today, Dr. Davis. Dr. Mellar Davis: Thank you. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/supportive-care-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

1
Therapy for Stage IV NSCLC With Driver Alterations: ASCO Living Guideline Update 2024.3 Part 2 15:20

39 weeks yang lalu15:20

15:20

Dr. Jyoti Patel is back on the podcast to discuss the updates to the living guideline on therapy for stage IV NSCLC with driver alterations. She shares updated recommendations in the first- and second-line settings for patients with stage IV NSCLC and classical EGFR mutations, and the impact of these updates for clinicians and patients. We also look to the future to discuss ongoing developments in the field. Read the full living guideline update " Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.3 " at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology , https://ascopubs.org/doi/10.1200/JCO-24-02785 Brittany Harvey: Welcome to the ASCO Guidelines Podcast , one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows including this one at asco.org/podcasts . My name is Brittany Harvey and today I'm interviewing Dr. Jyoti Patel from Northwestern University, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.3." It's great to have you back on the show today, Dr. Patel. Dr. Jyoti Patel: Thanks so much. Happy to be here. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Patel, who has joined us here today, are available online with the publication of the guideline and in the Journal of Clinical Oncology , which is linked in the show notes. So then, to dive into the content of this update, Dr. Patel, this clinical practice guideline for systemic therapy for patients with stage IV non small cell lung cancer with driver alterations is living, meaning that it's continuously reviewed and updated. So what data prompted this latest change to the recommendations? Dr. Jyoti Patel: Thanks so much. So it's really been an exciting time in the treatment of EGFR lung cancer, particularly this past year has required us to rethink approaches to front- and second-line therapy. In this particular update, we examined what patients in the front-line setting may be offered by their clinicians. And so we're talking about the population of classical EGFR mutations, so exon 19 and exon 21 L858R substitution. And so certainly for this population, osimertinib has a high level of evidence and should be offered to all patients at the time of diagnosis when they present with advanced disease. Our last update included a recommendation that patients could also get platinum doublet chemotherapy with osimertinib or osimertinib alone. This current recommendation also introduces another alternative therapy and that's the combination of amivantamab plus lazertinib. And so now, clinicians are faced with three really good options for their patients with EGFR exon19 deletion or L858R. Brittany Harvey: It's great to hear that there's this advance in the space, particularly for patients with these classical EGFR mutations that you mentioned. So what should clinicians know as they implement these new first-line recommendations? Dr. Jyoti Patel: I think it's become more complex than ever. Certainly, we know again that patients should get osimertinib in the frontline setting. But we've been kind of stuck at progression-free survival that's between a year and a half and two years. And so we've really been looking at opportunities to intensify therapy. So one could certainly be with chemotherapy or switching over to amivantamab, the bispecific antibody that targets EGFR and MET plus lazertinib, an oral TKI that's very similar in structure to osimertinib. And when you're talking to a patient, it's really a conversation about balancing efficacy with toxicity. Unfortunately, as we know, there aren't that many free lunches. And so if we think about what a patient is hoping for in their therapy and how we can further personalize treatment options, really is important to look at some of the analyses for this study. So in the study of amivantamab plus lazertinib, we know that there were increased toxicities with a combination of both therapies. In fact, up to 75% of patients had over grade 3 toxicities, versus about 43% of patients with osimertinib monotherapy. And we know if we look back at FLAURA2, almost two thirds of patients with osimertinib and chemotherapy had grade 3 toxicities, compared to 27% of patients with osimertinib alone. So we certainly see an increase in toxicities. Then we have to ask ourselves, are those paper toxicities or ones that really impact patients? And we know that amivantamab, for example, causes significant cutaneous toxicities. With both of these therapies, whether it's chemotherapy or adding amivantamab, there's the burden of infusional visits and increased time in the doctor's office. Certainly with chemotherapy, there can be an increased incidence of myelosuppression. And so when we're thinking about advising our patients, certainly we need to talk about the toxicities. But one thing that we've been able to do is to look at the patients that were included in this trial. And what we really find is that in higher risk cohorts, particularly those that we know historically have done less well with standard osimertinib, so patients, for example, with CNS metastasis, for those patients with co-mutations, it may be that that additive benefit is significant. And so one example I think would be from the MARIPOSA study, again, the study of amivantamab and lazertinib versus chemotherapy. What we can say is that patients who had co-mutations, so patients with EGFR mutations as well as TP53, lazertinib and amivantamab led to a hazard ratio of 0.65 compared to osimertinib alone. So that was 18.2 months versus 12.9 months. And so this may be really important to patients. And we also see conversely that patients with wild type TP53, so those patients who didn't have the mutation, probably had equivalent survival regardless of therapy. So certainly, we need to prospectively study some of these high-risk cohorts. We've only seen progression-free survival in these studies. And so at this juncture, we can advise our patients about toxicity, the improvements in certain categories of progression-free survival, but we really still don't know how this pans out in overall survival. In many of these studies, all patients do not necessarily cross over to the study arm and so they may have lost the benefit of subsequent therapy. Brittany Harvey: Absolutely. It's very important to talk about that balance of benefits and risks and particularly those toxicities that you discussed. So I appreciate reviewing that recommendation and the considerations for clinicians for first-line therapy. This update also included a second-line treatment update. What is that update for patients with EGFR alterations? Dr. Jyoti Patel: So this is where it gets super tricky because we have a frontline option with amivantamab and now we've had an update in the second line option. So what we said is that for patients who have progressed on an EGFR TKI, and in the United States, certainly that's predominantly osimertinib, or those in other parts of the world that may have gotten an earlier generation TKI, but do not have evidence of T790M or other targetable mutations, we can offer patients chemotherapy with or without amivantamab. And so certainly we have seen that this again leads to improved survival. There have also been a number of studies looking at incorporation of PD-L1 and anti-VEGF therapies. And what we can say, I think pretty clearly is that multiple phase 3 trials have really shown no benefit of the addition of PD-1 to platinum chemotherapy. But there are some emerging bispecific antibodies that may target PD-1 as well as VEGF, or combinations of antibodies that target both of those pathways that may improve outcome. At this juncture, I think we feel that the evidence surrounding chemotherapy plus amivantamab is strongest, but there is certainly work in this space that will be of interest. Now, what happens if your patient received amivantamab and lazertinib in the frontline setting and then has progression? And so we're trying to understand resistance mechanisms and opportunities for treatment. What the panel decided to recommend, based on the available evidence, was that certainly those patients should get platinum-based chemotherapy, but there may also be a role for antivascular endothelial growth factor targeting therapy such as bevacizumab in patients in whom it would be safe. Brittany Harvey: Great. I appreciate you detailing those recommendations when it gets complicated in the second-line setting. So what should clinicians know as they implement these second-line recommendations too? Dr. Jyoti Patel: So certainly the frontline setting matters significantly. So if a patient gets osimertinib in the frontline setting, we generally suggest that patients undergo repeat testing to see if they have another targetable mutation. If they don't, then I think preferred therapy would be chemotherapy with or without amivantamab. And amivantamab leads to a significant improvement in progression-free survival and response rate at the cost of increased risk of toxicity. For patients who get FLAURA2 in the frontline setting, chemotherapy plus osimertinib, it's a little bit of an unclear space. Those patients most likely would get docetaxel with or without ramucirumab. But there are other agents that we hope to have available to our patients in the near future. For patients who receive amivantamab and osimertinib, we recommend that those patients get chemotherapy probably with anti-VEGF as demonstrated by multiple trials that have shown the improved progression-free survival with introduction of an anti-VEGF agent. And we've seen evidence of amivantamab in the third line setting, so it is likely that this question about sequencing really takes center stage in our next set of trials. When you're talking to a patient, I think again, it's absolutely important to discuss: What are their goals? How symptomatic or how fast is their progression? Are there ways in which patients may benefit from spot treatment oligoprogression such as radiation? When is the right time for introduction of amivantamab and when do we think patients need chemotherapy? Is it up front or predominantly in the second-line setting? Brittany Harvey: Definitely. And then you've just touched on the goals of treatment for individual patients. So in your view, what does this update mean for patients with stage IV non-small cell lung cancer and an EGFR alteration? Dr. Jyoti Patel: For patients, this is a time in which shared decision making really needs to take center stage. So our best patients are those patients that are best informed not only about their disease but also have a good understanding about what is important to them and their families in terms of care. And so bringing that shared understanding to the table again helps us think about this particular cancer as more of a journey rather than just a one off treatment. Therapy will hopefully be prolonged, and so it's absolutely important that we address toxicities, make therapies more tolerable, again, with the shared goal of living long and living well. Brittany Harvey: Absolutely. Those are key points to making sure that patients are living both longer and have a good quality of life during that time as well. So then, before you mentioned the possibility of future sequencing trials and other ongoing developments. What additional studies or future directions is the panel examining for future updates to this living guideline? Dr. Jyoti Patel: So certainly we're thinking about trials that look at, for example, cfDNA clearance. So are there patients that do well and can we detect that early on without having to intensify therapy on day 1 so it may be that we add chemotherapy a little bit later. I think really exciting are some of the new bispecific. The HARMONi-A trial was a trial in China of a novel bispecific, ivonescimab. And this drug targets both PD-1 and VEGF and it was combined with chemotherapy. And this trial found almost a doubling of progression-free survival with this drug in combination chemotherapy in an EGFR patient population. That study is being planned and being run in the United States to see if we have similar outcomes with a more diverse population. So certainly that's exciting. There are a number of antibody drug conjugates that are being studied in the post-chemotherapy setting as well. And I think we'll likely soon see a better understanding of what co-mutations and burden of disease really mean when we're thinking about assigning treatment. So which patients, again, need intensification of therapy and which patients may do really well on just an oral agent that they're taking at home with more tolerable toxicity than dual treatment. Brittany Harvey: Yes, we'll look forward to continued developments in these fields and seeing some of those studies come to fruition. So with that, I want to thank you for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Patel. Dr. Jyoti Patel: Thanks so much, Brittany. It's really an exciting time for lung cancer and we hope that these updates really help physicians decide the best treatments for their patients. Again, it's a rapidly evolving landscape which is fantastic, but it does become more cumbersome to stay ahead of the literature. Brittany Harvey: Definitely. And so we appreciate your time and the panel's time spent reviewing this literature and providing this much needed information to clinicians everywhere. So finally, thank you to all of our listeners for tuning into the ASCO Guidelines podcast . To read the full guideline, go to www.asco.org/living-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.…

ASCO Guidelines

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Therapy for Stage IV NSCLC Without Driver Alterations: ASCO Living Guideline Update 2024.3 Part 1 10:48

39 weeks yang lalu10:48

10:48

Dr. Lyudmila Bazhenova joins us again to share the newest changes to the living guideline on therapy for stage IV NSCLC without driver alterations. She discusses new evidence reviewed by the panel and changes to second-line recommendations for patients with good performance status and HER2 overexpression, and what these updates mean in practice. We discuss ongoing evidence generation as we await further updates to these living guidelines. Read the full living guideline update " Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2024.3 " at www.asco.org/living-guidelines . TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines . Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology , https://ascopubs.org/doi/10.1200/JCO-24-02786 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts . My name is Brittany Harvey and today I'm interviewing Dr. Lyudmila Bazhenova from University of California San Diego Moores Cancer Center, co-chair on "Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2024.3." It's great to have you back on the show today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: It's my pleasure to be here as always. Brittany Harvey: Great. Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the entire guideline panel, including Dr. Bazhenova, who has joined us here today, are available online with the publication of the guide in the Journal of Clinical Oncology , which is linked in the show notes. So then to dive into the content here, first, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer without driver alterations has frequent updates to the recommendations. What prompted this latest update? Dr. Lyudmila Bazhenova: Living ASCO guidelines are created to keep up with rapidly changing evidence which affect treatment of our patients with lung cancer. As a committee, we review published literature on a specific topic at the regular intervals and determine if it alters any recommendations. This time, upon our literature review, we felt that there are new data that requires an update in the guidelines and therefore the guidelines were updated. Brittany Harvey: Great. Thank you for that updated information. So then it looks like the panel updated recommendations for second line and subsequent treatment options for patients with good performance status and HER2 overexpression. What is that updated recommendation from the panel? Dr. Lyudmila Bazhenova: Yes, this is correct. We now added an extra recommendation for patients with stage IV non-small cell lung cancer who have overexpression of the protein called HER2. HER2 overexpression with 2+/3+ level via immunohistochemistry is seen in approximately 8% to 20% of patients with lung cancer. And the data behind our recommendation comes from the DESTINY-Lung01 trial where patients with HER2 overexpression were treated with trastuzumab deruxtecan. And we saw that if patients with stage IV non-small cell lung cancer had a HER2 IHC score of 3+, overall response rate was seen at 53% and median duration of response was 6.9 months and, therefore, that in our opinion qualified for updated recommendation. We are still waiting for additional results that will be released later on another clinical trial where we see preliminary data presented at the World Conference of Lung Cancer in 2024. They looked at 36 patients also with HER2 overexpression and saw the overall response rate of almost 45%. It is important to highlight in this smaller study that a majority of the patients in the study were actually having EGFR mutation and the response rate in those patients who had an EGFR mutation was higher than the response rate in patients without EGFR mutations who just had a HER2 overexpression. So for now this is updated in the guidelines, but we will wait for additional data or formal publication of a World Lung Conference presentation and see if those recommendations need to be changed. Brittany Harvey: Understood, and I appreciate you providing the context of some of those ongoing developments as well. So then what should clinicians know as they implement this updated recommendation? Dr. Lyudmila Bazhenova: Number one, we should all start from remembering to test for HER2 via immunohistochemistry. There is a slight difference in what considers HER2 positive in lung versus breast. In lung, we use what's called the gastric scoring and the difference is the circumferential versus non circumferential staining of the membrane. And number two, immunohistochemistry is not always included in next generation sequencing panels. So when you order your next generation sequencing, I think it's important to know if your company that you're using is testing for HER2 via immunohistochemistry. And if it's not, make sure that you find a company that does or work with your local pathology department to make sure that this testing is offered. It is also important to know the difference between HER2 overexpression and HER2 exon 20 insertion mutation even though the treatment for those two abnormalities is the same, which is trastuzumab deruxtecan. But the benefit that you can cite your patients and the rigor of the literature supporting the usage of trastuzumab deruxtecan in mutation versus overexpression is different. Brittany Harvey: Yes. And as you mentioned, it's essential that, in the first place, patients are actually receiving the testing so that we know if they're eligible for these treatment options. So what additionally does this change mean for patients with stage IV non-small cell lung cancer and HER2 overexpression? Dr. Lyudmila Bazhenova: So for patients, it adds another treatment modality which is now FDA approved. So if there are patients listening to me, make sure that your physician has tested your tumor for HER2 overexpression. So I think proactive asking of your physician would be very appropriate in this situation. Brittany Harvey: Absolutely. And then earlier you mentioned an ongoing trial that the panel was looking to for the future. But what other additional trials did the panel review during this guideline update and what is the panel examining for future updates to this living guideline? Dr. Lyudmila Bazhenova: So at this point we reviewed three additional studies. The results of those studies did not make it into a change in guidelines. So we reviewed the HARMONi-2 trial. HARMONi-2 trial so far does not have an official publication and, as per our strategy on how we come up with ASCO guidelines, we need to wait for an official publication. So this is one thing we're going to be expecting in the future. Once this is published, we will review it and decide if we need to make an additional change in recommendations. For those of you who are not aware, HARMONi-2 trial used bispecific monoclonal antibody against VEGF and PD-1 and was a phase III randomized trial comparing their investigational product which is called ivonescimab over pembrolizumab for patients with PD-L1 more than 50. And again, we are waiting for the final publication to make our recommendation. The second trial we reviewed was a LUNAR trial and the LUNAR trial looked at addition of tumor treating fields to chemotherapy or immunotherapy in patients whose cancer progressed with platinum doublet. The key point about this study is that immunotherapy was not required to be administered in a first line setting which is a current standard of care in the United States. And even though the study met their primary endpoint of overall survival, there were more benefits in patients who were immunotherapy naive in the second line. And we felt that given the potential lifestyle implication of wearing a device for 18 hours per day, and the lack of evidence in immunotherapy-pretreated population, and the absence of data in the first-line setting where we currently using immunotherapy in the United States, we felt that there is insufficient data to definitely recommend addition of tumor treating fields to systemic chemotherapy for most patients. And we are waiting for additional trials that are ongoing in this setting to formalize or change our recommendations. And we also reviewed- the final study that we reviewed was TROPION-Lung01. TROPION-Lung01 study was a phase III study in post platinum doublet setting which compared efficacy of Dato-DXd and docetaxel and trials showed improvement in progression free survival but not in overall survival. And progression free survival benefit was more pronounced in non-squamous carcinoma histology subgroup and we felt that the results do appear promising, but the strength of evidence which was based on unplanned subgroup analysis was not sufficient enough to make a change in treatment recommendation at this time. Brittany Harvey: I appreciate your transparency on why some of that data did not prompt a change to recommendations at this time. And additionally, we'll look forward to those future published results and potential incorporation of new data into future versions of this living guideline. So, I want to thank you so much for your work to rapidly and continuously update this guideline and for your time today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: It is my pleasure. Thank you so much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/living-guidelines . You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store . If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.…

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