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1 APR

Systemic Treatment of Thyroid Cancer Guideline

Dr. Nabil Saba shares the first evidence-based guideline on thyroid cancer from ASCO. He highlights recommendations on first- and subsequent-line systemic treatment – including multikinase inhibitors (MKIs), genomically targeted therapies, immunotherapy, and cytotoxic chemotherapy across four subtypes of thyroid cancer: well-differentiated, differentiated high-grade or poorly differentiated, anaplastic, and medullary thyroid cancer. He dives into the evidence supporting each recommendation and explains the importance of shared decision-making on the risks and benefits of each treatment option. Dr. Saba also touches on outstanding questions including sequencing of agents, addressing resistance, emerging biomarker targets, and management of toxicities. Read the full guideline, "Systemic Treatment of Thyroid Cancer: ASCO Guideline." TRANSCRIPT This guideline, clinical tools and resources are available at https://ascopubs.org/topics/asco-guidelines/head-neck-cancer. 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. Nabil Saba from Emory University, lead author on "Systemic Treatment of Thyroid Cancer: ASCO Guideline." Thank you for being here today, Dr. Saba. Dr. Nabil Saba: Pleasure to be here. Brittany Harvey: And then just 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. Saba, 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 what we're here today to talk about, Dr. Saba, could you start us off by providing a general overview of the scope and purpose of this first ASCO guideline for thyroid cancer? Dr. Nabil Saba: So thyroid cancer is a complex disease, and the complexity has been added with the advent of multiple systemic therapeutic agents that have recently come on as part of the standard of care for treating this disease. The guidelines have lagged behind, I believe, in terms of being able to clearly delineate how to use these agents and what clinical settings to use them. And so this guideline, I think, is a much-needed and much-awaited guideline for clinicians to allow them to understand better the use of systemic agents in the treatment of thyroid cancer. And when we talk about systemic agents, what we want to specify is this applies mostly for patients with recurrent metastatic disease, patients who have failed the standard initial treatment, which continues to be surgical resection for these patients if surgery is possible, in addition to radioiodine therapy for the right clinical setting. Brittany Harvey: Absolutely. It's a good point that this patient population for this guideline focuses mainly on recurrent disease and patients who have already received surgery and radioactive iodine therapy. So then this guideline covers four subtypes of thyroid cancer, including well-differentiated, differentiated high-grade or poorly differentiated, anaplastic, and medullary thyroid cancer. As you mentioned, you address clinical questions on systemic therapies, including multikinase inhibitors, genomically targeted therapies, immunotherapy, and cytotoxic chemotherapy in both the first-line and subsequent lines for each of these subtypes. So I'd like to review the key recommendations by subtype. So first, what are the key points for systemic therapy for well-differentiated thyroid cancer? Dr. Nabil Saba: It's important to also stress the point that we have these different subtypes of thyroid cancer. So when we talk about radioiodine refractory, those are for patients who are candidates for radioiodine therapy, of course. This usually encompasses the well-differentiated thyroid cancer. So for this group of patients, the guideline focuses on whether the use of multikinase inhibitors compared to placebo or observation impacts the survival in the first-line setting, whether the use of targeted therapies compared to placebo impacts also the survival in the first-line setting, all in the radioiodine refractory setting, of course. And then we tackle the issue of immunotherapy because this also is a topic that has entered the realm, if you like, of thyroid cancer and is being used in some subtypes of thyroid cancer. So we thought it would be important to raise the question of the role of immunotherapy compared to targeted agents or multikinase inhibitors, in addition to the role of cytotoxic therapy or chemotherapy, as we say, in this patient population. So the guideline goes through all of these questions and then makes specific recommendations as to the use of some of the agents in the first-line setting and second-line setting in case these patients progress after first-line setting. So, for example, it's clear that for patients who are radioiodine refractory and who have well-differentiated thyroid cancer, multikinase inhibitors are centerpiece of the first-line treatment option. And for this patient population, the recommendation essentially is to use lenvatinib or sorafenib, even though lenvatinib is considered to be the first choice in this patient population in the first-line setting. For the subsequent line settings, patients should be offered cabozantinib, which has been also proven in randomized trials. As far as genomically targeted therapy, there is always the contention of whether these agents should be initiated first in case the patient has a genomically altered disease. And so, for example, if the patient has a RET alteration or NTRK alteration, the recommendation here is in favor of using RET-targeted therapies such as selpercatinib or NTRK-targeted therapies such as larotrectinib or entrectinib for these patients as a first-line setting. If they do have the BRAF alteration, which is a commonly seen alteration in these settings, the guideline essentially indicates that this may be offered initially prior to treatment with multikinase inhibitors as well, even though the quality of the evidence here is rather lower, and the strength of the recommendation is conditional. And so it's clear that multikinase inhibitors, in the absence of any of these genomic alterations, is really the first line, and then the question becomes when do we use these genomically targeted approaches in patients who have genomically altered disease? Which basically introduces also the complexity of the question here because we have multiple agents depending on these genomic findings. And then it is sometimes confusing for practitioners which one to use or what do we use first? And so I think the guideline provides clarity in terms of what is acceptable, what is rather not acceptable, what is based on a strong recommendation, what is based on a rather weaker recommendation. I think that's part of the value of such a guideline. And then finally we have the question of radioiodine well-differentiated and the question of immunotherapy as a first line. And here we do not recommend using immunotherapy for this patient population. For patients with subsequent line settings, potentially adding pembrolizumab to a multikinase inhibitor is mentioned, however the evidence is low, and the strength of the recommendation is also conditional here. As far as chemotherapy, this is not recommended in this day and age for this patient population, however it may be considered also in patients who fail or progress on genomically targeted therapy and/or multikinase inhibitors. So this is the summary of the recommendations for well-differentiated thyroid cancer, but certainly, for details, I would refer you to the actual guideline since there are many nuances that cannot be covered during just this discussion. Brittany Harvey: Certainly. The full guideline will be available for listeners in our show notes, and there are many recommendation tables and figures that can help folks as they think through these recommendations. A lot of those key points are really important as clinicians think through which systemic therapies to offer and sequencing of these agents, as you mentioned. Following those recommendations for well-differentiated thyroid cancer, what are the recommendation highlights for systemic therapy for differentiated high-grade or poorly differentiated thyroid carcinoma? Dr. Nabil Saba: This entity is rather a rare entity. It's important to stress the fact that this entity has not really been very well represented in clinical trials, and so when we talk about differentiated high-grade or poorly differentiated, the information here is limited. However, the guideline infers on the recommendations to this subtype of thyroid cancer based on what we know for other subtypes. And I think because of the strength of evidence we have in the well-differentiated and the anaplastic thyroid cancer, this guideline for this subgroup of patients draws from these two guidelines and sort of makes recommendations based on this. So in the first-line setting, of course, if patients don't have a genomically altered disease, we certainly would recommend lenvatinib or sorafenib like we do in the well-differentiated disease. For patients with genomically altered diseases, we follow sort of the same guideline as we have followed for the well-differentiated setting, with the caveat that the quality is rather lower here and the stren

1 Apr

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23 min
8 JAN

Expanding Treatment Options for Breast Cancer: ADCs and Oral SERDs

Dr. Monty Pal and Dr. Hope Rugo discuss advances in antibody-drug conjugates for various breast cancer types as well as treatment strategies in the new era of oral SERDs for HR-positive breast cancer. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and vice chair of academic affairs here at the City of Hope Comprehensive Cancer Center, Los Angeles. Today, I'm thrilled to be joined by Dr. Hope Rugo, an internationally renowned breast medical oncologist and my colleague here at City of Hope, where she leads the Women's Cancers Program and serves as division chief of breast medical oncology. Dr. Rugo is going to share with us exciting advances in antibody-drug conjugates (ADCs) that are expanding treatment options in various breast cancer types. She'll also address some of the complex questions arising in the new era of oral SERDs (selective estrogen receptor degraders) that are revolutionizing treatment in the hormone receptor-positive breast cancer space. Our full disclosures are available in the transcript of this episode. Dr. Rugo, welcome, and thanks so much for being on the podcast today. Dr. Hope Rugo: Thank you. Pleasure to be here. Dr. Monty Pal: So, I'm going to switch to first names if you don't mind. The first topic is actually a really exciting one, Hope, and this is antibody-drug conjugates. I don't know if I've ever shared this with you, but I actually started my training at UCLA, I was a med student and resident there, and it was in Dennis Slamon's lab. I worked very closely with Mark Pegram and a handful of others. This is right around the time I think a lot of HER2-directed therapies were really evolving initially in the clinics. Now we've got antibody-drug conjugates. Our audience is well-familiar with the mechanism there but tell us about how ADCs have really started to reshape therapy for HER2-positive breast cancer. Dr. Hope Rugo: Yeah, I mean, this is a really great place to start. I mean, we have had such major advances in breast cancer just this year, I think really changing the paradigm of treating patients. But HER2-positive disease, we've been used to having sequenced success of new agents. And I think the two biggest areas where we've made advances in HER2-positive disease, which were remarkably advanced this year in 2025, have been in antibody-drug conjugates with trastuzumab deruxtecan and with new oral tyrosine kinase inhibitors (TKIs) that have less of a target on EGFR and more on HER2, so they have an overall more tolerable toxicity profile and therefore a potentially better efficacy in the clinic. At least that's what we're seeing with these new strategies that we couldn't really pursue in the past because of toxicities of the oral TKIs. So, although our topic is ADCs, I'm going to include the TKI because it's so important in our thinking about treating HER2-positive disease. In the metastatic setting, we've seen these remarkable improvements in progression-free and overall survival in the second-line setting with T-DXd, or trastuzumab deruxtecan, compared to T-DM1. And then sequencing ADCs with giving T-DXd after T-DM1 was better than an oral tyrosine kinase or a trastuzumab combination with standard chemotherapy. That was DESTINY-Breast03 and DESTINY-Breast02. So, then we've had other trials since then, and T-DXd has moved into the early-stage setting, which I'll talk about in just a moment. But the next big trial for T-DXd in HER2-positive disease was moving it to the first-line setting to supplant what has become an established treatment for now quite a long time: the so-called CLEOPATRA regimen, which used the combined antibodies trastuzumab, pertuzumab with a taxane as first-line therapy. And then we've proceeded on with maintenance with ongoing HP for patients with responding or stable disease. And we'd seen long-term data showing, you know, at 8 years there was a group of patients whose cancers had never progressed and continued improved overall survival. So, T-DXd was studied in DESTINY-Breast09, either alone or in combination with pertuzumab compared to THP. The patient population had received a little bit more prior treatment, but interestingly, not a lot compared to CLEOPATRA. And they designed the trial to be T-DXd continued until progression with or without pertuzumab versus THP, which would go for six cycles and then stop around six cycles, and then stop and continue HP. Patients who had hormone receptor-positive disease could use hormone therapy, and this is one of the issues with this dataset because, surprisingly in this dataset and one other I'll mention, very few patients took hormone therapy. And even in the maintenance trial, the HER2CLIMB-05, less than 50% took hormone therapy as maintenance. This is kind of shocking to me and highlights an area of really important education, that outcome is improved when you add endocrine therapy for hormone receptor-positive HER2-positive metastatic disease in the maintenance phase, and it's a really important part of treatment. But suffice it to say, you know, you're kind of studying continued chemo versus stopping chemo in maintenance. And T-DXd, as we all expected, in combination with pertuzumab was superior to THP in terms of progression-free survival, really remarkably improved. And you could stop the chemo with toxicity, but most people continued it with T-DXd. Again, not a lot of people got hormone therapy, which is an issue, and you stop the chemo in the control arm. So, this has brought up a lot of interest in trying to use T-DXd as an induction and then go to maintenance, much as we do with the CLEOPATRA regimen with hormone therapy. But it brings up another issue. So first, T-DXd is superior; it's a great treatment. Not everybody needs to have it because we don't know whether it's better to give T-DXd first or second with progression - that we need a little bit longer follow-up. But just earlier this week, interestingly, the third week of December, the U.S. FDA approved T-DXd in the DESTINY-Breast09 approach with pertuzumab. So as I mentioned earlier, there was a T-DXd-alone arm; that arm has not yet reported. So very interesting, we don't know if you need pertuzumab or not. So what about the maintenance? That's the other area where we've made a huge advance here. So, we all want to stop chemo and we want to stop T-DXd. You don't want somebody being nauseated for two years while they're on treatment, and also there's a small number of patients with mostly de novo metastatic HER2-positive disease who are cured of their disease. We'd like to expand that, and I think these new drugs give us the opportunity to improve the number of patients who might be cured from metastatic disease. So the first maintenance study we saw was adding palbociclib, the CDK4/6 inhibitor, to endocrine therapy and HP, essentially. There, we had a remarkable improvement in progression-free survival difference of 15.2 months: 29 to 44 months, really huge. At San Antonio this year, we saw data with this oral tyrosine kinase inhibitor tucatinib, already showed it was great in a triplet, but as maintenance in combination with HP, it showed also a remarkable improvement in progression-free survival. But the numbers were all shifted down. So in PATINA, the control arm was in the 24-month range; here it was the tucatinib-HP arm that was in the 25 months and 16 months for control. So there was a differential benefit in ER-negative and ER-positive disease. So I think we're all thinking that our ideal approach moving forward would be to give T-DXd to most patients, we see how they do, and treat to best response. And then, stop the T-DXd, start HP, trastuzumab, pertuzumab for ER-negative, with tucatinib for ER-positive with palbociclib. We also have early data that suggests that both approaches may reduce the development of brain metastases, an issue in HER2-positive disease, and delay time to progression of brain metastases as seen in HER2CLIMB-05 in very early data - small numbers, but still quite intriguing that you might delay progression of brain metastases with tucatinib that clearly has efficacy in the brain. So, I think that this is a hugely exciting advance for our patients, and these approaches are quickly moving into the early stage setting. T-DXd compared to standard chemo, essentially followed by THP, so a sequenced approach resulted in more pathologic complete responses than a standard THP-AC-type neoadjuvant therapy. T-DXd alone for eight cycles wasn't better, and that's interesting. We still need the sequenced non-cross-resistant chemo. But I think even more importantly, the data from DESTINY-Breast05 looking at T-DXd versus T-DM1 in patients with residual disease after neoadjuvant HER2-targeted therapy showed a remarkable improvement in invasive disease-free survival with T-DXd versus T-DM1, and quite early. It was a high-risk population, higher risk than the T-DM1 trial with KATHERINE, but earlier readout with a remarkable improvement in outcome. We expect to be FDA approved sometime in the first half of 2026. So then we'll get patients who've already had T-DXd who get metastatic disease. But my hope is that with T-DXd, maybe with tucatinib in the right group of patients or even sequenced in very high-risk disease, that we could cure many more patients with early-stage HER2-positive breast cancer and cure a subset, a greater subset of patients with de novo metastatic disease. Dr. Monty Pal: That's brilliant. And you tackled so many questions that I was going to follow up with there: brain metastases, etc. That was sort of looming in my mind. I mean, general thoughts on an ADC versus a TKI in the context of brain mets? Dr. Hope Rugo: Yeah, it's an interesting question because T-DXd has shown quite good efficacy in this setting. And tucatinib, of course, had a trial where they took patients with new brain mets, s

8 Jan

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27 min
10 MAR

Patient-Clinician Communication Guideline Update

Dr. Timothy Gilligan and Dr. Calvin Chou discuss the updated guideline on patient-clinician communication in oncology. They highlight clinical recommendations and strategies on topics such as communication skills and practices that apply at every visit, principles for telehealth interactions, cross-disciplinary communication, facilitating involvement of the patient's support network, discussing prognosis, goals of care, treatment selection – including clinical trials, end-of-life discussions, overcoming barriers to communication, facilitating discussions of cost of care and financial toxicity, mitigating stigma, and setting boundaries with patients. Dr. Gilligan and Dr. Chou also share how clinicians can enhance their communication skills through skills practice opportunities and experiential learning. They discuss how fundamental communication is to optimal patient care and look to the future on how generative AI may impact healthcare communication. Read the full guideline, "Patient-Clinician Communication: ASCO Guideline Update" 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 Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-26-00118 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. Timothy Gilligan from Taussig Cancer Institute and the Center for Excellence in Healthcare Communication at Cleveland Clinic, and Dr. Calvin Chou from the University of California and Veterans Affairs Health Care System in San Francisco, co-chairs on "Patient-Clinician Communication: ASCO Guideline Update." Thank you for being here today, Dr. Gilligan and Dr. Chou. Dr. Timothy Gilligan: Thank you for having us. Dr. Calvin Chou: Delighted to be here. 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. Gilligan and Dr. Chou 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 I would like to dive into what we are here really today to talk about. So Dr. Gilligan, this guideline updates the patient-clinician communication guideline that was first published in 2017. What prompted this update and what is the scope of this updated guideline? Dr. Timothy Gilligan: So I think with the first guideline, that was the first draft of it that we published five or six, seven years ago, really we were focused on getting the content right, what was the state of the knowledge at that time, and I was very happy with what came out of that. But when I looked back on it, I thought there were ways we could make it more accessible and more practical. Because what we really would like would be for people to apply what we know and then communicate more effectively with patients and colleagues. And one of the reasons I was really excited on the membership of the panel we had this time was I thought they were very well selected to help us do that, is to really think about what are practical guidelines, practical steps we can tell people to take that will improve their own experience and the experience of patients and the quality of care. Brittany Harvey: Absolutely, thinking about operationalizing that guideline really improves the dissemination and the uptake of these recommendations. So then, Dr. Chou, I would like to review the key recommendations and strategies across the clinical questions that the guideline addressed. I realize today with our limited time we may not be able to go through every recommendation and strategy, so we will start with some of the highlights. First, let's address the highlights of the process of communication with patients and their support networks. This includes the questions that address what communication skills and practices apply at every visit across the continuum of care, principles for telehealth interactions, cross-disciplinary communication, and facilitating involvement of the patient's support network. In your view, what are the most important recommendations across these clinical questions? Dr. Calvin Chou: I think the thing that all clinicians know in their bones that they want to be able to do effectively with patients is to communicate information clearly, as well as to communicate in a way that really deepens the relationship, demonstrates empathy, and also demonstrates understanding bilaterally between the various parties. So the communication guidelines that we established in this group, they are fundamental to communication in all conversations throughout healthcare. And the first guideline talks about how clinicians and their team can communicate effectively with the patient and the patient's support network. And those include things like preparing ahead of time; getting a list of the topics that are important to the patient support network so that we can consider them in the visit; making certain that we are hearing what the patients' and the patients' support networks are saying very, very closely; responding to those empathically; and being able to have conversations about care throughout the visit that demonstrate respect and deepen the trust; and then finally, to have some kind of bidirectional understanding, usually through teach-back, that allow both sides to know that communication has occurred as opposed to just been downloaded. The guidelines also talk about applying these same communication skills throughout telehealth communication - that is both in terms of synchronous communication, audio or video, as well as asynchronous communication, i.e., through secure messaging. We also talk about how we can use these same communication skills to communicate effectively with members of our own team. Interprofessional communication is an important part of all the work that we do, and how we can use these very, very same skills in communication with colleagues, with nursing staff, with social workers, and other allied health professionals. These are all very, very important, crucial members of our healthcare team in the delivery of care to our patients. And that is something that we really need to emphasize throughout to try to bring the best of communication in every conversation that we have. Dr. Timothy Gilligan: I totally agree with that. Those are really important points. When I was looking over it in preparation for this podcast, it struck me that we have a lot of recommendations and a lot of small things that we can do either well or not well. And it reminded me of a quotation from a famous chef, Marco Pierre White, who said that perfection is a lot of little things done well. This guideline has a lot of little things that if you do them well, you get better outcomes. And I think the chef's point was that if you want a really delicious dish, you have to pay attention to all those little details. And I think if people go through the guidelines carefully and apply the skills that are along the lines of what Dr. Chou was talking about, we get better results. And those results are really important results. It is not only patient satisfaction, which is really important, but it is also quality of care and outcomes for patients. It is better medical care. It is a better day for us, we have a better day if we have better conversations. Poor communication creates endless headaches for everybody. What I see in the guidelines is it is a lot of little best practices and it requires discipline to learn those. The good news is none of them I don't think are all that hard. The bad news is doing it consistently well every day requires discipline and practice. And what I would hope for these guidelines is that people will read them carefully and think about what they can do to apply what we know more consistently. And I think the interprofessional communication piece, that was something we added this year, is really critical. Medicine has a bad history of really disrespectful behavior. It was almost normalized that different specialties would make fun of each other, that different professions would talk disrespectfully of each other. And we know now that uncivil behavior results in more healthcare errors. And it is not only bad for our teams and our culture, but it is bad for our patients if we are not communicating well with each other. So I thought it was really critical that we added that piece to the update. Brittany Harvey: Absolutely. Those fundamental principles that Dr. Chou outlined are really key across every healthcare interaction, including those interdisciplinary interactions. And as you alluded to, Dr. Gilligan, I think it will really serve clinicians well to review the details and go through every table to read the recommendations and each individual strategy to help them improve their communication in day-to-day interactions. Moving to some of those day-to-day clinical communication scenarios, Dr. Gilligan, I'd like to think through some of those key points. So what is recommended for discussion of prognosis, goals of care, treatment selection, including discussion of clinical trials, and end-of-life discussions? Dr. Timothy Gilligan: So my perspective is that there is a broad theme of flattening the hierarchy that runs through these recommendations and this part of the guid

10 Mar

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31 min
26 JAN

Highlights From the 2026 ASCO GI Cancers Symposium

Dr. Monty Pal and Dr. Mary Feng discuss the latest advances in metastatic colorectal, gastric, and gastroesophageal cancers that were presented at the 2026 ASCO Gastrointestinal Cancers Symposium.

26 Jan

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20 min
10/04/2025

Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer Guideline Update

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

10/04/2025

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21 min
26 FEB

Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer Guideline Update

Dr. Lakshmi Rajdev and Dr. Manish Shah join the podcast to discuss the updated guideline on immunotherapy and targeted therapy in unresectable locally advanced, advanced, or metastatic gastroesophageal cancer. They share first-line and subsequent-line recommendations for both gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma based on actionable biomarkers including PD-L1 expression, MMR and/or MSI, CLDN18.2 expression, and HER2 status. They note the importance of the algorithms and tables in the guidelines that provide visual illustrations and quick reference guides of the evidence-based recommendations. They also comment on ongoing and recently presented trials that may impact future guidelines in this space. Read the full guideline, "Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update" at www.asco.org/gastrointestinal-cancer-guidelines" TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/gastrointestinal-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-25-02958 Timestamps · 00:00 – 02:15 Introduction and Overview · 02:16 - 08:20 First-line treatment for patients with pMMR/MSS, HER2-negative gastroesophageal adenocarcinoma · 08:21 –10:29 First-line treatment for patients with pMMR/MSS, HER2-positive gastroesophageal adenocarcinoma · 10:30 – 14:39 First-line treatment for patients with dMMR/MSI-H, gastroesophageal adenocarcinoma · 14:40 – 18:03 First-line treatment for ESCC · 18:04 – 22:04 Second- and third-line therapy for gastroesophageal adenocarcinoma and ESCC · 22:05 – 24:38 Importance of guideline · 24:39 – 27:45 Outstanding questions and future research 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. Lakshmi Rajdev from the Icahn School of Medicine at Mount Sinai and Dr. Manish Shah from Weill Cornell Medicine, co-chairs on "Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update." Thank you for being here today, Dr. Rajdev and Dr. Shah. Dr. Lakshmi Rajdev: Thank you. Dr. Manish Shah: Thank you for having us. It is wonderful. 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. Rajdev and Dr. Shah, 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 dive into what we are here today to talk about, Dr. Shah, I would like to start first with what prompted the update to this guideline, which was previously published in 2023, and what is the scope of this updated guideline? Dr. Manish Shah: Yes, terrific. So even in the last few years, the pace of drug development in gastroesophageal cancers has just been astounding. So, what prompted this guideline is actually the practice-changing results for a new biomarker, CLDN18.2 hat was based on the GLOW and SPOTLIGHT studies, as well as a practice-changing study in HER2-positive disease where we added pembrolizumab to trastuzumab and chemotherapy for tumors that are HER2-positive and PD-L1 CPS 1 or greater. And then there were also new studies and new approvals in esophageal squamous cell cancer that you will hear about as well. So there were several studies, overall more than 5,000 patients were reported on, and that led to several new therapies, new indications, and it really necessitated this guideline. Brittany Harvey: Excellent. It is great to hear about all of these exciting updates in this space. So then to next review the key recommendations of this guideline by clinical question that the expert panel addressed. So, Dr. Rajdev, what is the recommended first-line treatment for patients with proficient mismatch repair, microsatellite stable, HER2-negative gastroesophageal adenocarcinoma? Dr. Lakshmi Rajdev: Thank you for that question. So historically, we have sort of used fluoropyrimidine and platinum doublets, which yielded a survival of about one year. More recently, immunotherapy and targeted therapy options have improved outcomes in patients with advanced esophageal and gastric adenocarcinoma, as well as squamous cell carcinoma. Patients with gastric and GE junction adenocarcinoma have a high rate of actionable alterations, so it is imperative that physicians test the following biomarkers upfront so that it can help guide therapy. The markers recommended by the ASCO panel are HER2, MMR or MSI, CLDN18.2, and PD-L1. And also, it was recommended to use NGS if feasible in this patient population. HER2, as we know, is expressed in about 15% to 25% of patients; PD-L1 expression occurs in about 80% of patients; MSI-high, deficient MMR is present in about 5% to 8% of patients; and CLDN18.2 expression is present in about 40% of patients. There is, of course, biomarker overlap. About 13% to 22% of CLDN18.2 patients are also PD-L1 positive. For patients with pMMR or microsatellite stable HER2-negative disease with PD-L1 expression greater than 1 and absence of CLDN18.2, the panel recommended a first-line therapy with fluoropyrimidine and platinum-based therapy in combination with immunotherapy. These recommendations stem from large phase 3 trials, and the agents approved in the United States are pembrolizumab, nivolumab, and tislelizumab. It has been shown that immunotherapy benefit is greater in patients with higher PD-L1 expression, and it is not possible to comment on the individual PD-L1 cutoff scores and sort of identify the optimal PD-L1 cutoff score that sort of balances benefits and harms. But what is recommended is that immunotherapy-based treatments can be offered in patients with a CPS score of greater than 1. With regard to the choice of immunotherapy agents, that is pembrolizumab, nivolumab, or tislelizumab, these agents are considered to have similar efficacy, and the selection of an agent could be based on dosing schedule, cost considerations, toxicity, and the method of administration. Typically, clinicians should avoid withholding the start of chemotherapy while awaiting biomarker testing, depending on the clinical scenario. Now, for patients with pMMR microsatellite stable disease that is HER2-negative with PD-L1 expression less than 1 and positive CLDN18.2 expression, zolbetuximab-based treatments or in combination with chemotherapy is recommended, and this is based on two global phase III randomized controlled trials, the GLOW and the SPOTLIGHT. And across both studies, the hazard ratio for the overall survival was 0.78, and similarly, there was also an improvement in progression-free survival favoring the zolbetuximab group compared to the chemotherapy group alone. An important note is that nausea, vomiting is commonly associated with zolbetuximab-based treatments, and the panel recommended prophylactic antiemetics, adjusting zolbetuximab infusion rates, pausing infusion temporarily, using non-prophylactic antiemetics, and hydration intravenously prior to discontinuation of zolbetuximab-based chemotherapy. So effective handling of the GI-related symptoms with zolbetuximab is recommended prior to discontinuation of therapy. Now, for patients with pMMR microsatellite stable HER2-negative gastric, GE junction adenocarcinoma with PD-L1 expression greater than 1 and CLDN18.2 positivity, the ones with the dual expression with CLDN18.2 as well as PD-L1 chemotherapy, the choice of therapy can be based on the degree of PD-L1 expression, the toxicity profile, the burden of symptoms, and the anticipated improvement in symptoms associated with response to treatment, the patient comorbidities, the prior medical and treatment history. So this decision needs to be made on a case-by-case basis, and these are some of the factors that we suggested that could potentially influence the choice of therapy. For patients with pMMR microsatellite stable disease that is HER2-negative and a PD-L1 expression less than 1 and an absence of CLDN18.2 expression, first-line therapy with fluoropyrimidine and platinum-based chemotherapy is recommended. So you can see we have segmented out patients based on PD-L1 expression, pMMR and microsatellite stable disease expression, and also based on CLDN expression. Brittany Harvey: Absolutely. And that first point you noted, I think is really important, that biomarker testing is really critical for treatment decision-making in this space. So then the next subgroup of patients that the panel looked at, Dr. Shah, what first-line therapy is recommended for patients with proficient mismatch repair, microsatellite stable, HER2-positive gastroesophageal adenocarcinoma? Dr. Manish Shah: So this was an update from a few years ago. So we have known for 15 years now that if you are HER2-positive, you should get trastuzumab plus chemotherapy. That was based on the ToGA trial. And the update now is based on a trial called KEYNOTE-811, where it examined the addition of pembrolizumab to trastuzumab and chemotherapy versus trastuzumab and chemotherapy, and there was a progression-free and overall survival benefit. And again, here, the biomarkers are important. If your CPS PD-L1 is l

26 Feb

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29 min
10/12/2021

Abemaciclib with Endocrine Therapy in the Treatment of High-Risk Early Breast Cancer: ASCO Optimal Adjuvant Chemotherapy and Targeted Therapy Guideline Rapid Recommendation Update

An interview with Dr. Sharon Giordano, co-chair on "Abemaciclib with Endocrine Therapy in the Treatment of High-Risk Early Breast Cancer: ASCO Optimal Adjuvant Chemotherapy and Targeted Therapy Guideline Rapid Recommendation Update." Dr. Giordano discusses the results and impact of the monarchE trial, the updated recommendations on the use of abemaciclib, and impact for clinicians and patients. For more information, visit www.asco.org/breast-cancer-guidelines.

10/12/2021

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9 min
19 FEB

Personalizing Treatment in Head and Neck Cancers

Dr. Monty Pal and Dr. Ari Rosenberg discuss the evolution of treatment strategies in head and neck cancers, including the challenges of treating both HPV-positive and HPV-negative disease and the emergence of blood-based biomarkers to advance personalized therapy across different subtypes. TRANSCRIPT Dr. Monty Pal: Hello and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist, professor, and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, we're going to explore the evolving landscape of treatment strategies in head and neck cancer management, including locoregionally advanced head and neck squamous cell carcinoma, which happens to be on the rise in United States, in part due to spike in HPV-mediated oropharyngeal cancers. We're also going to discuss the emerging strategies of using blood-based biomarkers to really advance personalized therapy. Joining me for this discussion is Dr. Ari Rosenberg. He's a medical oncologist focused on head and neck cancer, and he's an associate professor – congratulations on the recent promotion – at the University of Chicago. The University of Chicago has really produced luminaries in this field, Dr. Rosenberg included. I've had the pleasure of getting to know Dr. Ezra Cohen over the years, who really had his grounding there, and of course Everett Vokes, former ASCO President. I'm really looking forward to this conversation, Ari. Thanks so much for joining us. Dr. Ari Rosenberg: Thanks, Monty. Thanks for the invitation. Dr. Monty Pal: You got it. And just a quick note for our listeners, our full disclosures are going to be in the transcript at the end of this episode. So let's start with the basics, if you don't mind. So, head and neck cancers are very diverse and they're challenging, right? In the sense that they're near vital organs, the treatments, you know, as we all saw during fellowship, if not now in clinical practice. They can really have such a major impact on vital organ function, speech, swallowing, et cetera. Can you just comment on head and neck cancers that are on the rise in the U.S.? I alluded to this briefly. Particularly, we've heard this in the context of colorectal cancer and so forth. Are you actually seeing younger adults being affected by this? Dr. Ari Rosenberg: Yeah, thanks for that. The vast majority of head and neck cancers are head and neck squamous cell carcinomas, as I'm sure many of the listeners recall as well from fellowship or their current training. And as you alluded to, the organ function, long-term and functional quality of life outcomes are quite important, particularly in the context that these develop in high value real estate, parts of our head and neck area that we use for speaking, swallowing, all sorts of other essential functions as well. As you also alluded to, we think of this in two different particular subtypes of head and neck cancer. The historical head and neck cancer from 50, 60 years ago was almost exclusively related to carcinogen exposure, tobacco, alcohol use, and that subtype of carcinogen-induced head and neck cancer has been slowly declining. However, over the last now several decades, we've been seeing an increase in primary oropharyngeal squamous cell carcinoma, mostly tonsil, base of tongue. These are attributable to HPV, human papillomavirus exposure. And that's now the majority of the head and neck cancers that we tend to see in our clinic. As you also alluded to, these have very different prognoses as well. HPV-related head and neck cancer has a much more favorable prognosis where much of the interest has been in can we de-intensify to optimize long-term function? But then the non-HPV-related head and neck cancer, or what we call HPV-negative head and neck cancer, continue to be very, very challenging. We only managed to cure about half of these folks, with many of these patients developing the current disease. These patients, in addition to being difficult to treat, also have major impacts both in terms of the treatments they undergo as well as their disease that can impact their function and quality of life. And you hinted at this a little bit, but we have been seeing an increase in younger patients with HPV-negative head and neck cancer as well, which is quite concerning. Younger patients, oftentimes never smokers, never drinkers, who are developing non-HPV-negative head and neck cancer. And that's been a little bit of a more recent trend that we've been seeing as well. So, definitely a lot of work to be done to optimize and improve outcomes across all of these different head and neck cancer subtypes. Dr. Monty Pal: I mean, I'm just curious, you know, in the context of colorectal cancer, one of the things that we talk about is the potential role of the microbiome driving some of these young-onset cancers with, you know, perhaps there being an impact on, for instance, inflammation and the gut and what have you. Tell me about head and neck cancer. Is this anything known as to why younger patients might be getting diagnosed with non-HPV type cancers? It's odd to me. Dr. Ari Rosenberg: Yeah, it's a great question. A lot of people are working on it. I think we folks have hypotheses, but it hasn't totally panned out exactly what's going on there. It does have a little bit more of a tendency towards women, whereas historically head and neck cancer is much more common in men than it is in women. But lots of people working on that, whether it's related to chronic inflammation, whether it's related to the microbiome. Whether it's related to dental exposure, dental work. So, a lot of folks trying to parse that out because I agree with you, it needs to be identified alongside improving treatment paradigms for these patients, the young ones and the older patients as well. Dr. Monty Pal: Interesting, interesting. You know, one of the phenomena that was sort of coming around when I was in training 25 years ago was this role of sort of induction therapy for head and neck cancers. And of course, it's really come full circle now to include checkpoint inhibitors and so forth. Tell me a little bit about this and how you apply it, maybe in an HPV-mediated context, maybe in a non-HPV context. Dr. Ari Rosenberg: Yeah, absolutely. Induction chemotherapy, as you alluded to, or neoadjuvant chemotherapy, depending on what the locoregional treatment approach is. Similar to other cancer types where systemic control early on has many potential advantages in this setting. Now, in head and neck cancer, even though induction chemotherapy is quite active in head and neck cancer, both HPV-positive and HPV-negative with pretty good response rates. A survival advantage for all comers with local regionally advanced disease remains unproven. There's been two randomized trials, both underpowered, but essentially did not show a survival advantage, showing that induction chemotherapy for all patients with locoregionally advanced and neck cancer can't be justified for a survival advantage. That being said though, there remains a number of potential advantages of giving induction or neoadjuvant chemotherapy, of course, improving systemic control and debulking the disease early on has potential advantages, and predicting the responsiveness to subsequent radiation treatment. We know for some time in head and neck cancer that the percentage of shrinkage or the response to induction chemotherapy actually predicts outcome related to radiation as a dynamic biomarker where response can be used to select patients, for example, for de-escalated radiation has been an area of active investigation, active research. And it also remains a key opportunity to evaluate predictive biomarkers and understanding pre and post treatment to better understand the biology. I'll just add to your question that recently over this past year, we also saw phase 3 data for neoadjuvant immunotherapy for a subset of head and neck cancer that is surgically resectable. And so that's reintroducing the potential benefit in the immunotherapy era of incorporating immunotherapy in the neoadjuvant or the induction setting as part of the evolving treatment paradigm for these diseases. Dr. Monty Pal: That's really interesting. And you kind of alluded to already several topics that I plan to hit on, you know, for instance, the role of immune checkpoint inhibitors, induction, chemotherapy, and so forth. And you started to touch on biomarkers. And of course, I think that's something near and dear to many of us in academic oncology. One thing that we've started talking a lot about in the context of colorectal cancer is circulating tumor DNA. How do you think this might fit in the context of head and neck cancer? Can you give us a flavor for that? Dr. Ari Rosenberg: Yeah, absolutely. In head and neck cancer, the current landscape is most developed for circulating tumor DNA for HPV-related head and neck cancer. The advantage of HPV-related head neck cancer is that you have a distinctive HPV DNA that does tend to spill out into the peripheral blood and can be detected using various different blood-based assays. And because of that advantage as a tissue agnostic approach, it turns out that a number of HPV DNA plasma assays are actually quite sensitive and quite specific. And a number of them have indeed been commercialized. Of course, not only for detecting a baseline, but also grading responsiveness during treatment and probably most importantly in the post-treatment surveillance setting, the detection of HPV DNA in the plasma remains a very important and substantial predictor of developing recurrent disease. There's been a number of trials that have been emerging looking at ctDNA and HPV-related head and neck cancer, using it, for example, as a strategy to deescalate patients. That was something we saw this past ASCO from the Dana-Farber group, and also using it to early det

19 Feb

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21 min
16/12/2024

Systemic Therapy for Stage I-III A**l Squamous Cell Carcinoma Guideline

Dr. Van Morris presents the new evidence-based guideline on systemic therapy for localized a**l squamous cell carcinoma. Dr. Morris discusses the key recommendations from the Expert Panel, including recommended radiosensitizing chemotherapy agents, dosing and schedule recommendations, the role of induction chemotherapy and ongoing adjuvant chemotherapy, and considerations for special populations. He emphasizes the importance of this first guideline from ASCO on a**l squamous cell carcinoma for both clinicians and patients with stage I-III a**l cancer, and ongoing research the panel is looking to for the future. Read the full guideline, "Systemic Therapy for Stage I-III A**l Squamous Cell Carcinoma: ASCO Guideline" at www.asco.org/gastrointestinal-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/gastrointestinal-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-24-02120 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. Van Morris from MD Anderson Cancer Center, co-chair on "Systemic Therapy for Stage I-III A**l Squamous Cell Carcinoma: ASCO Guideline." Thank you for being here today, Dr. Morris. Dr. Van Morris: Thank you for having me. On behalf of our committee who put together the guidelines, I'm really excited to be here and talk with you today. 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 guideline panel, including Dr. Morris, 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 jump into the content of this guideline, Dr. Morris, can you provide an overview of both the purpose and the scope of this guideline on stage I to III a**l squamous cell carcinoma? Dr. Van Morris: So a**l cancer is considered a rare malignancy for patients in the United States and across the world as well. Even though it's not something we see as commonly, for example, as the adjacent colorectal cancer, this still is a cancer that is rising in incidence every year in the United States. And really, despite the presence of the preventative HPV vaccines, which we hope will ultimately prevent and eradicate this cancer, we still expect the incidence to continue to rise in the coming decades before we really start seeing numbers begin to decrease as a result of the vaccine. So this is an alarming trend for which oncologists will continue to see likely more and more cases and new diagnoses every year. So we wanted to review the most recent literature and provide oncologists up to date recommendations for how they can best take care of patients with a new diagnosis of localized a**l cancer. Brittany Harvey: Absolutely. I appreciate that background and context to set the stage for this guideline. So then next I'd like to review the key recommendations of this guideline. So starting from the first clinical question, what are the recommended radiosensitizing, doublet or single chemotherapy agents for patients with stage I to III a**l cancer? Dr. Van Morris: It's true that really the standard treatment for patients with localized a**l cancer has not changed over the last literally half century. When the Nigro regimen was first reported back in 1974, 50 years ago, the standard of care for patients with a new diagnosis of localized a**l cancer centers around concurrent chemotherapy and radiotherapy. And we looked at the various randomized control trials and the highest level of evidence which has been reported over the past decades, and really for most patients, the standard of care continues to remain doublet cytotoxic chemotherapy in combination with radiation. We reported that the most commonly, and I think most accepted, regimen here is a combination regimen of 5-FU, intravenous 5-fluorouracil with mitomycin C. And this most commonly is given on a week 1 to 5 regimen. The 5-FU, we recommended a dose of 1000 milligrams per meter squared per day on days 1 to 4 and then on days 29 to 32 of the radiation treatment. And then the mitomycin C, looking at various trials, has been given at a dose of 10 milligrams per meter squared on day 1 and day 29, or alternatively a single dose of mitomycin C at 12 milligrams per meter squared on day 1. I think that the thing that's important for clinicians and patients alike to remember is that this chemotherapy can be very toxic in patients who are undergoing a curative-intent therapy for this diagnosis of localized a**l cancer. I think it's just important for oncologists to be watching closely the blood counts for the patients to make sure that the myelosuppression doesn't get too bad. And then in select cases, if that is the case, when the oncologist opts to go for the day 1 and day 29 dosing, it may be prudent, if the myelosuppression is too excessive, to consider withholding that day 29 dose. Brittany Harvey: Great. Thank you for providing those recommendations along with some of those dosing and the schedule recommendations from the expert panel. So are there any other alternate dose or schedule recommendations from the expert panel? Dr. Van Morris: Yeah, but I think that we saw with the ACT II data that was a randomized trial that was done out of the UK that compared 5-FU mitomycin with 5-FU cisplatin as two different doublet cytotoxic regimens, that overall outcomes were very similar between the two regimens in terms of curative outcomes for patients treated whether 5-FU mitomycin or 5-FU cisplatin. So certainly there is evidence supporting the use of cisplatin as a second cytotoxic agent with 5-fluorouracil. In the ACT II study that was given at a dose of 60 milligrams per meter squared on days 1 and 29 along with the 5-FU at the regimen I talked about previously. There is other lower level of evidence data suggesting that even the 5-FU and cisplatin can be given on a weekly schedule and that that can be safe. Actually, at my institution at MD Anderson, that is our standard practice pattern as well. There's also the option when we're thinking about giving pelvic radiation for patients with lower GI cancers, many oncologists in the treatment of localized rectal adenocarcinoma are accustomed to using capecitabine as a chemosensitizer in patients with localized rectal cancer. If I'm giving chemoradiation for a patient with localized a**l cancer, can I substitute the intravenous 5-FU with oral capecitabine? And although the evidence is not as strong in terms of available data with regards to randomized controlled trials, there certainly is data that suggests that capecitabine may be an acceptable alternative in lieu of intravenous 5-fluorouracil that would be given at a dose of 825 milligrams per meter squared on days of radiation. But certainly, I think that that's a feasible approach as well and maybe even associated with less hematologic toxicity than intravenous 5-FU would be. Brittany Harvey: Great. It's important to understand all the options that are out there for patients with early-stage a**l squamous cell carcinoma. So in addition to those chemoradiation recommendations, what is recommended from the expert panel regarding induction chemotherapy or ongoing adjuvant chemotherapy for this patient population? Dr. Van Morris: When we think about treating patients with lower GI cancers with curative intent therapies, when we think about the more common rectal adenocarcinoma, oncologists may be used to giving chemoradiation followed by subsequent cytotoxic chemotherapy. But actually when you look at the data for a**l cancer, really there's not any data that strongly supports the use of either induction chemotherapy prior to chemoradiation or adjuvant post-chemoradiation chemotherapy. The RTOG 98-11 study was a trial which evaluated the role of induction 5-fluorouracil prior to chemoradiation and did not show any survival benefit or improved outcomes with the use of induction chemotherapy in a randomized control trial setting. The ACT II trial, which I referenced earlier, was a 2 x 2 design where patients were either randomized to concurrent chemoradiation with 5-FU mitomycin C or concurrent chemoradiation with 5-FU cisplatin. But then there was a second randomization after chemoradiation where half of the study participants received adjuvant cisplatin 5-fluorouracil after completion of their chemo radiation, or the other half were randomized to the standard of care, which of course would be observation. And what that trial showed was that there was no added benefit with the addition of post-chemoradiation cytotoxic chemotherapy. So we look at these data and say that in general, for the general population of patients with localized stages I to III a**l cancer, there really is no supporting data suggesting benefit of either induction chemotherapy or adjuvant chemotherapy. And to that end, really it's concurrent chemoradiation remains the standard of care at this time for patients with a new diagnosis of localized a**l cancer. Brittany Harvey: Absolutely. It's just as important to know what is not recommended as it is to know what is recommended for these patients. And so I thank you for explaining the evidence behind that decision from the panel as well. So then, are there any other considerations for special populations

16/12/2024

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16 min
26/06/2025

Innovations in GU Cancer Treatment at ASCO25

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss important advances in the treatment of prostate, bladder, and kidney cancers that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News. I am delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of the GU Center at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode. Jeanny, it is great to have you on the podcast. Dr. Jeanny Aragon-Ching: Oh, thank you so much, Neeraj. Dr. Neeraj Agarwal: Jeanny, let's begin with some prostate cancer abstracts. Let's begin with Abstract 5017 titled, "Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer." Can you walk us through the design and the key findings of this first-in-human trial? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this study, presented by Dr. Capucine Baldini, introduces pasritamig, a first-in-class T-cell redirecting bispecific antibody that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. KLK2 is also known as human kallikrein 2, which is selectively expressed in prostate tissue. And for reference, KLK3 is what we now know as the PSA, prostate-specific antigen, therefore making it an attractive and specific target for therapeutic engagement. Now, while this was an early, first-in-human, phase 1 study, it enrolled 174 heavily pretreated metastatic CRPC patients. So many were previously treated with ARPIs, taxanes, and radioligand therapy. So given the phase 1 nature of this study, the primary objective was to determine the safety and the RP2D, which is the recommended phase 2 dose. Secondary objectives included preliminary assessment of antitumor activity. So, pasritamig was generally well tolerated. There were no treatment-related deaths. Serious adverse events were rare. And in the RP2D safety cohort, where patients received the step-up dosing up to 300 mg of IV every 6 weeks, the most common treatment-related adverse events were low-grade infusion reactions. There was fatigue and grade 1 cytokine release syndrome, what we call CRS. And no cases of neurotoxicity, or what we call ICANS, the immune effector cell-associated neurotoxicity syndrome, reported. Importantly, the CRS occurred in just about 8.9% of patients. All were grade 1. No patients required tocilizumab or discontinued treatment due to adverse events. So, this suggests a favorable safety profile, allowing hopefully for outpatient administration without hospitalization, which will be very important when we're thinking about bispecifics moving forward. In terms of efficacy, pasritamig showed promising activity. About 42.4% of evaluable patients achieved a PSA50 response. Radiographic PFS was about 6.8 months. And among patients with measurable disease, the objective response rate was about 16.1% in those with lymph node or bone metastases, and about 3.7% in those with visceral disease, with a median duration of response of about 11.3 months. So, altogether, this data suggests that pasritamig may offer a well-tolerated and active new potential option for patients with metastatic CRPC. Again, as a reminder, with the caveat that this is still an early phase 1 study. Dr. Neeraj Agarwal: Thank you, Jeanny. These are promising results for a bispecific T-cell engager, pasritamig, in prostate cancer. I agree, the safety and durability observed here stand out, and this opens the door for further development, possibly even in earlier disease settings. So, shifting now from immunotherapy to the evolving role of genomics in prostate cancer. So let's discuss Abstract 5094, a real-world, retrospective analysis exploring the prognostic impact of homologous recombination repair gene mutations, especially BRCA1 and BRCA2 mutations, in metastatic hormone-sensitive prostate cancer. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So this study was presented by Dr. David Olmos, represents one of the largest real-world analyses we have evaluating the impact of homologous recombination repair, or what we would call HRR, alterations in metastatic hormone-sensitive prostate cancer. So, this cohort included 556 men who underwent paired germline and somatic testing. Now, about 30% of patients had HRR alterations, with about 12% harboring BRCA1 or BRCA2 mutations and 16% having alterations in other HRR genes. Importantly, patients were stratified via CHAARTED disease volume, and outcomes were examined across treatment approaches, including ADT alone, doublet therapy, and triplet therapy. The prevalence of BRCA and HRR alterations were about similar between the metastatic hormone-sensitive prostate cancer and the metastatic castrate-resistant prostate cancer, with no differences observed, actually, between the patients with high volume versus low volume disease. So, the key finding was that BRCA and HRR alterations were associated with poor clinical outcomes in metastatic hormone-sensitive prostate cancer. And notably, the impact of these alterations may actually be even greater in metastatic hormone-sensitive prostate cancer than previously reported in metastatic CRPC. So, the data showed that when BRCA mutations are present, the impact of the volume of disease is actually limited. So, poor outcomes were observed across the board for both high-volume and low-volume groups. So, the analysis showed that patients with HRR alterations had significantly worse outcomes compared to patients without HRR alterations. Median radiographic progression-free survival was about 20.5 months for the HRR-altered patients versus 30.6 months for the non-HRR patients, with a hazard ratio of 1.6. Median overall survival was 39 months for HRR-altered patients compared to 55.7 months for the non-HRR patients, with a hazard ratio of 1.5. Similar significant differences were observed when BRCA-mutant patients were compared with patients harboring non-BRCA HRR mutations. Overall, poor outcomes were independent of treatment of ARPI or taxanes. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data reinforce homologous recombination repair mutations as both a predictive and prognostic biomarker, not only in the mCRPC, but also in the metastatic hormone-sensitive setting as well. It also makes a strong case for incorporating genomic testing early in the disease course and not waiting until our patients have castration-resistant disease. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. And I think this really brings home the point and the lead up to the AMPLITUDE trial, which is LBA5006, a phase 3 trial that builds on this very concept of testing with a PARP inhibitor, niraparib, in the hormone-sensitive space. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the AMPLITUDE trial, a phase 3 trial presented by Dr. Gerhardt Attard, enrolled 696 patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. 56% of these patients had BRCA1 and BRCA2 mutations. Patients were randomized to receive abiraterone with or without niraparib, a PARP inhibitor. The majority of patients, 78% of these patients, had high-volume metastatic hormone-sensitive prostate cancer, and 87% of these patients had de novo metastatic HSPC. And 16% of these patients received prior docetaxel, which was allowed in the clinical trial. So, with a median follow-up of nearly 31 months, radiographic progression-free survival was significantly prolonged with the niraparib plus abiraterone combination, and median was not reached in this arm, compared to abiraterone alone, which was 29.5 months, with a hazard ratio of 0.63, translating to a 37% reduction in risk of progression or death. This benefit was even more pronounced in the BRCA1 and BRCA2 subgroup, with a 48% reduction in risk of progression, with a hazard ratio of 0.52. Time to symptomatic progression also improved significantly across all patients, including patients with BRCA1, BRCA2, and HRR mutations. Although overall survival data remain immature, early trends favored the niraparib plus abiraterone combination. The safety profile was consistent with prior PARP inhibitor studies, with grade 3 or higher anemia and hypertension were more common but manageable. Treatment discontinuation due to adverse events remained low at 11%, suggesting that timely dose modifications when our patients experience grade 3 side effects may allow our patients to continue treatment without discontinuation. These findings support niraparib plus abiraterone as a potential new standard of care in our patients with metastatic hormone-sensitive prostate cancer with HRR alterations, and especially in those who had BRCA1 and BRCA2 mutations. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. This trial is especially exciting because it brings PARP inhibitors earlier into the treatment paradigm. Dr. Neeraj Agarwal: Exactly. And it is exciting to see the effect of PARP inhibitors in the earlier setting. So Jeanny, now let's switch gears a bit to bladder cancer, which also saw several impactful studies. Could you tell us about Abstract 4502, an exploratory analysis from the EV-302 trial, which led to approval of enfortumab vedotin plus pembrolizumab for our patients with newly diagnosed metastatic bladder cancer? So here, the authors looked at the outcomes in patients who achieved a confirmed complete response wit

26/06/2025

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30 min

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