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Dr. Monty Pal and Dr. Vamsi Velcheti discuss the evolving treatment landscape in EGFR-mutated non-small cell lung cancer, including landmark trials like FLAURA2, novel drug therapies, and the growing importance of ctDNA and MRD testing. 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 professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, I'm truly delighted to introduce Dr. Vamsi Velcheti, who's a professor of medicine and the chief of hematology-oncology at the Mayo Clinic in Jacksonville, Florida. We'll be discussing the expanding treatment landscape in EGFR-positive lung cancer and how to navigate the challenges of balancing treatment efficacy, toxicity, and patient quality of life in the EGFR-positive space. Just FYI, our full disclosures are available in the transcript of this episode. Vamsi, it's so great to have you on the podcast. Thank you so much for being here. Dr. Vamsi Velcheti: Thank you, Monty. It's a pleasure to be here with you. It's a really exciting topic and there are a lot of updates in the EGFR space. Dr. Monty Pal: So, I'm going to need your help with this because I'll be honest with you, I see very little lung cancer, if any, in my practice. I'm pretty much exclusively kidney cancer these days. I'm coming on 20 years at City of Hope now, and I still remember when trials like ECOG 1599 were presented with, you know, platinum doublets. And, of course, the field has changed a lot since then. But tell us a little bit about the first-line landscape, and I think just for the sake of time, we're going to stick with EGFR-positive disease here. What does it look like these days? Dr. Vamsi Velcheti: Monty, the foundation of care remains the third-generation EGFR inhibitors. These are selective EGFR inhibitors, like osimertinib. We've had an evolution of the development of these TKIs. Like, you know, we had the first-generation, second-generation, not-so-selective EGFR inhibitors. Now we have mutant-selective EGFR inhibitors in the clinic, and they're doing a really good job. And these are quite effective in patients who have classical activating mutations. But the reality is that these have not been transformative. These agents have fundamentally changed the response patterns, excellent CNS penetration, and very good tolerability profile. However, we don't see a lot of durability in terms of the response. So, what's different today is now there have been several trials in combination with these third-generation EGFR inhibitors that have really laid the foundation of how we kind of think about EGFR-positive disease. At the high level, there are a lot of challenges to selecting the patients for these combination-based modalities. I'm assuming we'll be talking more about these different trials and different approaches. Some of these combination-based strategies have really moved the needle in terms of improving overall survival and really improving long-term outcomes and durability in our patients. Dr. Monty Pal: And we are going to get into the weeds on this in just a moment. But I did kick off this podcast talking about chemotherapy, ECOG 1599. It does seem as though chemotherapy is still a component of management in advanced non-small cell lung cancer. So, can you tell us about, perhaps first, you mentioned osimertinib, you know, some of these next-generation EGFR inhibitors. Tell us about the role of chemo plus osimertinib. Dr. Vamsi Velcheti: That's exactly where I was going with the combination-based strategies. You know, we first started off with our earlier trials in the EGFR space evaluating the question of, are targeted therapies, are these highly effective, third-generation, EGFR-selective inhibitors, superior to platinum-doublet chemotherapy? And we've had multiple trials demonstrating that, like the FLAURA trial and in the past with second-generation EGFR inhibitors like erlotinib and gefitinib and afatinib. So, we know that these TKIs actually perform better than platinum-doublet chemotherapy. Now, we have a large, global, phase 3 trial data from the FLAURA2 trial, which looks at the question, "Hey, you know, osimertinib is better than chemotherapy, platinum-doublet chemotherapy. Can we do even better by combining osimertinib with platinum-doublet chemotherapy?" So, FLAURA2 answered that question. This is a large, phase 3 trial, and it's a positive trial with improved durability of disease control and improving overall survival with combination with chemotherapy. So, it's a very important and landmark trial, and essentially combining osimertinib with a platinum-based chemotherapy improved responses, deepened responses, and improved overall survival and really changing the disease trajectory. And this strategy is definitely compelling, especially in patients who have certain clinical high-risk features like, you know, patients who have high disease burden or patients who are sometimes having rapid disease progression early on osimertinib, especially with patients who have a lot of visceral disease burden. So, intensifying treatments up front could alter the natural trajectory of the disease. Dr. Monty Pal: So, you sort of alluded to this in that last part there, but is that kind of how you in clinical practice select? Is it based on, you know, visceral involvement? Is it based on rapidity of disease where you think about adding chemotherapy to osimertinib? Maybe you can give us the corollary. Which patients do you just use osimertinib alone in, for instance? Dr. Vamsi Velcheti: Definitely, there are some patients who have low disease burden and they have the classical mutations, like an exon 19 deletion. And these patients, especially if they don't have a lot of disease burden, they don't have CNS involvement, there may be a subset of patients who could just do fine on osimertinib of course, with close monitoring of the disease. I guess we'll get into that later, how do we do that with either ctDNA or like closer imaging or both. So, there may be some opportunity to kind of escalate patients' treatments based on certain clinical characteristics or radiographic characteristics or certain biological characteristics informed by ctDNA or other approaches. Dr. Monty Pal: No, that's interesting. And you're right, we will chat about ctDNA in just a bit. But before we get there, I think one of the big agents that has really sort of come to the fore in advanced non-small cell lung cancer is amivantamab. I've heard a lot about this in the context of even kidney cancer because in certain subsets, I'm interested in MET-directed therapies and so forth, right? So maybe tell us a little bit about the mechanism of amivantamab first, and then maybe tell us about this pivotal MARIPOSA trial where it's combined with lazertinib. Dr. Vamsi Velcheti: So, the MARIPOSA trial compared lazertinib alone with amivantamab plus lazertinib. And this trial demonstrated overall survival advantage, and there were key differences in terms of tolerability and the safety of amivantamab, which is an EGFR and MET bispecific, and there were certain kind of unique toxicity profiles that make it a little different than the intensification approach with chemotherapy through the FLAURA2 trial. So, there's a trade-off in terms of the toxicity profile. It's a different agent and a different management protocol in terms of dermatological toxicity management that clinicians need to be comfortable with. And also, there are certain unique issues in terms of amivantamab; there's a higher rate of infusion-related reactions, there's an increased risk for edema and VTEs because of amivantamab. Certainly a different toxicity profile, different management paradigm there in terms of longitudinal care of these patients requiring dermatological care and like, you know, close monitoring and prophylaxis VTEs. But having said that, definitely it's a different strategy, and it kind of changes the biology and the natural history of the cancers, and we do see some durability of responses that we see with the MARIPOSA. So, it's certainly a great alternative, at least for some patients. Dr. Monty Pal: That was a great overview of MARIPOSA. Now comes the really difficult question, which is, how do you choose between the two? You have these two great options, right, for EGFR-positive patients. You've already highlighted some of the distinctions in terms of toxicity. I think the audience is well aware of the side effects of chemo-doublet, perhaps even the EGFR-based therapies. Amivantamab is quite new. Give us a sense of how you in clinical practice decide between the two potential options here. Dr. Vamsi Velcheti: Yeah, I think that's the big challenge. I think these are two independent strategies that have evolved through the phase 3, and both of them have demonstrated overall survival benefit. So, the way I think about this is in three dimensions, right? Like, the disease biology, the patient priorities, and feasibility of care delivery. So, when I talk about the disease biology, you know, the mechanism is very different, and MET is a very dominant driver of disease in EGFR-altered patients and it's a significant mechanism of resistance, acquired resistance to TKIs. So, certainly I think there's a patient population that could benefit from a MET-directed therapy up front. However, we don't have great data to kind of really demonstrate how using amivantamab in the front line is going to change that. And are there like perhaps like some patients who we could identify who would benefit from such a strategy? Very recently, there have been some approvals in the second-line setting in lung cancer, not in the EGFR space, but like in generally in lung cancer, with the MET ADCs, and those drugs are approved with a companion diagnostic, which requires MET IHC testing. So, what has happened, at least in large academic practices and also I think in the community now, they have been checking for MET IHC expression more routinely in lung cancer. What we have been doing in our institution is we have been doing MET IHC as a reflex for all patients with EGFR, not just EGFR, but all non-small cell lung cancer patients. What that has done is now, like, we have been increasingly testing patients with EGFR for MET. And there's clearly a subset of patients who have de novo MET expression and a high MET expression. And those patients, I've been kind of like preferentially treating them with the MARIPOSA regimen. But again, I have to caution the audience that we still don't have data that MET IHC is going to help us make those decisions, whether it's better than like a FLAURA2 regimen. But however, in the second-line setting in the CHRYSALIS trial, we know that MET is a very powerful predictor of response to amivantamab. We really need more data there, but that's what I have been doing in my practice. But also, there's a lot of patient preference here. Like, there are some patients who don't want chemotherapy, and they want a non-chemotherapy approach. So, certainly there are some patients who prefer to have amivantamab. And now with the amivantamab, the subcutaneous version, the infusion reactions and the logistics of actual administration of amivantamab are more favorable with the subcutaneous approval. So, those are some of the elements that we need to take into account. Dr. Monty Pal: Well, I want to hone in on that because this subcutaneous administration route has been a big debate that I've seen on social media. Tell us, how much easier does it actually make the amivantamab experience? Does it cut down on the rash? Is it just infusion reactions? What's been your clinical experience? Vamsi Velcheti, MD: So, the subcutaneous administration of amivantamab has definitely improved the infusion reaction issue. Very rarely patients have infusion reaction now with the subcutaneous injections. And also, the infusion time is much, much shorter. Like we don't need a lot of infusion time, which is sometimes a challenge in busy infusion clinics. We need to take that into account. As far as the impact of the subcutaneous formulation on dermatological toxicity, we haven't really seen significant difference in terms of the intensity or rates of dermatological toxicity with subcutaneous. The benefits are really with the infusion reaction, the ease of administration. And interestingly, in the PALOMA trial, it also seems to be, even though this was not the primary endpoint of the study, there seems to be some suggestion that the subcutaneous amivantamab seems to have improved OS compared to the IV amivantamab. We don't really understand why, but that's a finding from the trial that's very intriguing. Dr. Monty Pal: That is really fascinating. I'm kind of curious to see how that's going to pan out. I'm going to shift gears a little bit here. And, you know, as we sort of close, I wanted to talk a little bit about biomarkers. I mean, this is obviously not a lung cancer-specific issue. It's something we think about across the board. But what I will say is that there are certain commonalities, and in bladder cancer, we think a lot now about ctDNA. But you've been way ahead of the game in lung cancer. Tell us how you guys use ctDNA, maybe both from the standpoint of monitoring for mutational status, but if you can, maybe offer some insights into some of these new MRD tests that are available too. Dr. Vamsi Velcheti: Yeah, it's rapidly evolving. Certainly, I think in the lung cancer space, you know, this has really kicked off in the lung cancer space with incorporating ctDNA into the workflow. Of course, you know, like baseline evaluation, we still kind of heavily rely on tissue genomic sequencing. But as you know, with targeted therapy, a lot of these patients have disease that evolves over time, and changes in terms of mutational pattern driving acquired resistance is a major issue across different molecular subtypes. And especially so in EGFR, when there are certain actionable opportunities associated with that transformation. So, we need to kind of have like a longitudinal snapshot of how we monitor these patients. So, the ctDNA has come to be like a tool that has now come to the forefront of clinical workflow, and almost all my patients who are having disease progression have ctDNA for kind of evaluating for resistance and informing treatment decisions, especially in EGFR. But having said that, there are a lot of challenges in terms of using ctDNA as a tool for monitoring. There are a lot of different types of assays and different platforms, and being able to use this as a quantitative tool that would be used along with the CT scans that we routinely use in clinical practice has been a challenge. And I think I would love to hear your perspectives as well, Monty, about how you're thinking about that in bladder and other disease contexts. But having said that, I think there's a lot of opportunity to incorporate ctDNA and MRD assays into clinical decision-making. Right now, in terms of clinical trials and clinical development, there have been some very interesting trials that are currently ongoing, especially in the EGFR space. We know that patients who clear ctDNA, based on some retrospective data and also like some retrospective-prospective data from trials that have already read out, that patients who clear ctDNA early with target therapy tend to do much better. They have a longer durability of response. There may be a subset of patients who have, even though they're having radiographic response, they have persistent ctDNA after a certain time point of initiation of targeted therapy. Those patients may require escalation of therapy. We don't yet know. I can't recommend that as a standard right now because we don't have clinical evidence to support that. But however, some of the clinical trials, like the ELIOS trial that's being done right now, that's actually completed enrollment, we'll hopefully see the results very soon. So, there is an emerging thought that instead of intensifying treatment for all patients with EGFR, there may be a population that may be just fine with frontline osimertinib monotherapy and introducing the intensification strategy at the time of emergence of MRD or progression on ctDNA before radiographic progression. So, there are a lot of adaptive molecular response criteria that we are kind of exploring in clinical trials that could inform how the future is going to look like for EGFR and other perhaps targeted therapies as well. So, it's fascinating, and I think there's a lot of opportunity there. Dr. Monty Pal: You know, you asked for my perspective. I actually think that what you highlighted there is the most interesting opportunity for ctDNA: the ability to de-escalate therapy. In terms of drug development, we've done so much to bring new therapies to patients, and now it's a bit of an embarrassment of riches, but the downside is that I feel like we tend to overtreat a lot of patients in the clinic. So, I definitely view MRD, you know, some of these other ctDNA techniques with methylation and so forth that may not be sort of tumor-dependent or bespoke could be incredibly, incredibly helpful. You touched on sort of the future, right, in this last section here with biomarkers. But give us a sense now in terms of novel drug therapies in the EGFR space. What are you most excited about moving forward in 2026 and beyond? Dr. Vamsi Velcheti: Yeah, I think there's a lot going on in this space, and not just this space, but across lung cancer and others as well. Like looking at the next generation of targets for ADCs. And I think a lot of these have to do with…so far in the drug development space, as you know, the improvements in clinical outcomes has been very incremental. So, we really need to make that big leap. And I think the big leap is not going to come from, in my opinion, from the next ADC, but it's going to come from how we tailor treatments and how we monitor disease better and how do we kind of incorporate the next treatment earlier and not wait for the radiographic progression. So, there's a lot of opportunity there to integrate biomarkers and dynamic biomarkers into clinical trial design and incorporating the recent advances in terms of drug design. You know, we have a lot of assets in the EGFR space, the next-generation EGFR inhibitors that are kind of designed with resistance in mind and rational combination, knowing when to introduce those combinations is also equally important. So, there's a lot going on, really exciting times to be in drug development. The one thing that I really hope will come to the forefront in drug development, not just for lung cancer, but all disease groups, is to kind of really be thoughtful about how we incorporate these really cool molecular monitoring tools and creating a composite score with imaging to be able to like really design the next generation of clinical trials. Dr. Monty Pal: You're so spot-on with that. I definitely think that we're getting to this point where, you know, we could think about the next BiTE, the next CAR-T, the next ADC. But, you know, maybe it's time for us to start really honing in on appropriate applications of these drugs, honing in on the right dose and what have you, because I definitely see some issues there. Vamsi, this has just been terrific. I really want to thank you so much for sharing your fantastic insights with us today on the ASCO Daily News Podcast, and I really appreciate all your efforts to move the field of lung cancer forward. Dr. Vamsi Velcheti: Thanks, Monty. I really enjoyed the conversation. Dr. Monty Pal: Yeah, this was terrific. And thanks to our listeners as well. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: 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. Follow today's speakers: Dr. Monty Pal @montypal Dr. Vamsi Velcheti @VamsiVelcheti Follow ASCO on social media: ASCO on X ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Monty Pal: Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis Dr. Vamsi Velcheti: Honoraria: Galvanize Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, AstraZeneca/MedImmune, GSK, Amgen, Taiho Oncology, Novocure, Regeneron, Takeda, Janssen Oncology, Picture Health Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline
In this episode of Lung Cancer Considered, host Dr. Narjust Florez and guest Dr. Sam Rosner examine controversies around antibody-drug conjugates (ADCs) live from the 2026 Targeted Therapies of Lung Cancer (TTLC) conference. Guest: Sam Rosner, MD Assistant Professor of Medicine, University of Maryland School of Medicine Thoracic Medical Oncologist, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
In today's episode, we spoke with Eric K. Singhi, MD. Dr Singhi is an assistant professor in the departments of general oncology and thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center in Houston.Antibody-drug conjugates (ADCs) are rapidly emerging as one of the most exciting therapeutic advances in lung cancer. In this episode, Singhi explored how TROP2-directed ADCs are beginning to reshape treatment strategies across both non–small cell and small cell lung cancer.Singhi discussed where these agents currently fit within the treatment algorithm for EGFR-mutant non–small cell lung cancer, including the recent accelerated approval of datopotamab deruxtecan-dlnk (Datroway; Dato-DXd) and the evolving clinical data supporting its use after progression on targeted therapy and platinum-based chemotherapy. He also examined emerging evidence for other TROP2-targeting agents such as sacituzumab tirumotecan (sac-TMT) and what early trial results suggest about response rates and future treatment sequencing.Beyond efficacy, Singhi highlighted the practical considerations oncologists must navigate as ADCs enter routine practice, from managing chemotherapy-like toxicities to monitoring for unique adverse effects such as stomatitis, ocular effects, and interstitial lung disease.In our exclusive interview, Dr Singhi discussed where agents like dato-DXd and sac-TMT may fit in evolving treatment algorithms, the clinical data driving their momentum, and what oncologists should consider as these therapies move closer to routine practice in lung cancer.
Long-time Microsoft MVP and consultant Richard Hicks joins The PowerShell Podcast to talk about ADCS security, PKI misconfigurations, and why PowerShell is a consultant's ultimate force multiplier. Richard shares real-world stories from auditing enterprise certificate environments, explains how simple template mistakes can lead to full domain compromise, and walks through tools like Locksmith that help administrators quickly identify dangerous configurations. The conversation also explores Richard's open-source PowerShell work, including his widely downloaded Get-UEFICertificate script for Secure Boot certificate expiration issues and his new ADPrincipalCertificate module for cleaning up unnecessary certificates published in Active Directory. Along the way, Richard reflects on career growth, publishing, consulting, and why sharing knowledge openly has been one of the biggest drivers of his long-term success. Key Takeaways: • ADCS is easy to deploy but difficult to secure — Misconfigured certificate templates, especially ESC1 scenarios, can allow instant privilege escalation and domain compromise. • PowerShell turns repetitive work into reusable tools — From UEFI certificate auditing to Active Directory cleanup, scripting creates consistency and prevents human error. • Sharing expertise compounds over time — Blogging, publishing modules, and speaking at conferences builds credibility, community, and long-term career momentum. Guest Bio: Richard Hicks is the founder and principal consultant of Richard M. Hicks Consulting, Inc. A Microsoft MVP with over 30 years of experience, he specializes in secure remote access and PKI, helping organizations deliver secure, high-performing access for today's mobile workforce. Resource Links: Richard Hicks Website – https://richardhicks.com Connect with Richard – https://richardhicks.com/connect Connect with Andrew: https://andrewpla.tech/links Get-UEFICertificate Script – https://www.powershellgallery.com/packages/Get-UEFICertificate ADPrincipalCertificate Module – https://www.powershellgallery.com/packages/ADPrincipalCertificate Locksmith ADCS Audit Tool – https://github.com/jakehildreth/Locksmith PDQ Discord – https://discord.gg/PDQ PowerShell Wednesdays – https://www.youtube.com/watch?v=Oa0GYX9_vj8&list=PL1mL90yFExsix-L0havb8SbZXoYRPol0B&pp=sAgC The PowerShell Podcast on YouTube: https://youtu.be/4HYCAjQS2W8
Welcome to the Oncology Brothers podcast! In this episode, we dived into the evolving frontline treatment landscape for triple-negative breast cancer (TNBC). Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ Join us as we welcomed Dr. Sherene Loi, a leading breast medical oncologist from Australia, to discuss the challenges of treating TNBC and the exciting new treatment options available. We explored the significance of PD-L1 scoring in metastatic TNBC, the implications of recent trials like ASCENT-04, and the potential of antibody-drug conjugates (ADCs) such as sacituzumab govitecan and datopotamab deruxtecan. Key topics included: • The role of PD-L1 positivity in treatment decisions • Insights from the ASCENT-04 trial and its findings • Common side effects associated with sacituzumab and strategies for management • The future of immunotherapy and ADCs in TNBC treatment Whether you're a healthcare professional or someone interested in the latest advancements in oncology, this episode is packed with valuable information and clinical pearls. Don't forget to subscribe for more insightful discussions on cancer treatment! #TNBC, #PDL1positive, #ASCENT04, #Immunotherapy, #OncBrothers
Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we're diving into some pivotal advancements and strategic shifts within the industry, highlighting how these changes are shaping the future of patient care and drug development.Let's start with Bristol Myers Squibb, which has been making headlines with its latest success in the realm of antibody-drug conjugates (ADCs). The company's ADC has reached an important milestone in a Phase 3 breast cancer trial conducted in China. This study successfully met its dual primary survival endpoints, affirming the company's significant $800 million investment in this promising drug candidate. The potential of ADCs in oncology cannot be overstated; they offer a remarkable combination of targeted therapy by harnessing the specificity of antibodies alongside the cytotoxic power of traditional chemotherapy. This approach not only enhances precision in treatment but also minimizes collateral damage to healthy tissues, showcasing the transformative potential of ADCs in cancer therapy.On the regulatory front, there are ongoing discussions about the impact of political decisions on drug pricing and innovation. The Trump administration's Most Favored Nation drug pricing policy has stirred significant concern within the biotech sector. In response, ten midsize biotech firms have united to form the Midsized Biotech Alliance of America to challenge this policy. They argue that such pricing strategies could hinder innovation by enforcing restrictive pricing models, potentially stalling the development pipeline for new therapies that address unmet medical needs.In terms of strategic corporate movements, Boehringer Ingelheim has entered into a $500 million partnership with a British biotech firm aimed at developing an oral therapy for autoimmune diseases. This collaboration is part of a broader trend towards precision medicine which focuses on modulating specific immune cells to improve treatment outcomes while minimizing unwanted side effects. It's a clear indication that companies are increasingly investing in targeted therapies that promise better efficacy and patient safety. Additionally, Boehringer Ingelheim's partnership with Sitryx underscores another trend: strategic partnerships aimed at innovative research endeavors with substantial investment commitments—potentially exceeding $500 million—to explore immune response modulation.The acquisition landscape is also seeing dynamic shifts. Asahi Kasei's acquisition of Germany's AiCuris for $920 million marks a strategic move to enhance its R&D capabilities, specifically focusing on antiviral therapies for immunocompromised patients. This acquisition aligns with growing global attention towards infectious disease research, especially in a post-pandemic era where preparedness and rapid response capabilities have become paramount.Meanwhile, Sarepta Therapeutics is undergoing a significant leadership change as CEO Doug Ingram announces his retirement. Ingram's leadership was characterized by notable advancements in treatments for Duchenne muscular dystrophy (DMD), although it wasn't without its share of challenges regarding regulatory and pricing debates. As Sarepta continues to expand its gene therapy pipeline, this leadership transition comes at a crucial juncture, potentially setting new directions for the company's future.Accent Therapeutics' recent decision to halt its solid tumor trial due to adverse events exemplifies the risks inherent in drug development. The company is now redirecting its focus towards other cancer programs, illustrating how adaptability remains key in navigating clinical setbacks.Protagonist Therapeutics has made a strategic choice by accepting a $400 million payment from Takeda instead of sharing profits from its hematology asset rusfertide. This decision may provideSupport the show
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 less than 1, we would not recommend Pembrolizumab in that setting, so you would still get trastuzumab and chemotherapy. But if it is 1 or greater, the PD-L1 CPS score, then we do recommend pembrolizumab unless there is a contraindication to immunotherapy. The take-home message really is from the onset of diagnosis, please check your biomarkers. And I will just, it is worth repeating, it is important to check your PD-L1 status, HER2 status, mismatch repair status, and CLDN18.2 status. And then the optimal therapy, and it is outlined in the publication, is really biomarker-driven. We know that if we are able to hit the target that is overexpressed, we are going to have a better outcome. And Dr. Rajdev did mention where there is overlap, there can be a lack of data, and that is where we are with both PD-L1 positive and CLDN positive. Here we do have data in HER2-positive cases where if you are both HER2-positive and PD-L1 positive, you would combine trastuzumab and pembrolizumab for the best outcomes. Brittany Harvey: Understood. I really appreciate you detailing what is most important for each individual biomarker combination that patients may have. So then following that, Dr. Rajdev, what does the expert panel recommend for first-line treatment for patients with esophageal squamous cell carcinoma that is not amenable to definitive chemoradiation? Dr. Lakshmi Rajdev: There are three phase III randomized clinical trials that have influenced practice in patients with esophageal squamous cell carcinoma examining the benefit of immunotherapy in this patient population. The RATIONALE-306 was a randomized trial of tislelizumab plus chemotherapy with platinum and fluoropyrimidine or paclitaxel versus placebo with chemotherapy. And then you have the KEYNOTE-590, which compared pembrolizumab plus chemotherapy versus chemotherapy alone. And then you have CheckMate-648, which included comparisons of nivolumab plus chemotherapy versus nivolumab plus ipilimumab or chemotherapy. And the primary endpoints for these studies were overall survival, and they did look at subgroups with PD-L1 expression. They used TPS score greater than 1% in CheckMate-648 and PD-L1 CPS greater than 10 in KEYNOTE-590. The bottom line is that the overall hazard ratio for overall survival across this patient population was 0.72. So clearly, there is benefit in patients that express PD-L1 CPS greater than 1 for benefit for the addition of immunotherapy. Now, the benefit again in patients with a PD-L1 expression less than 1 remains limited, and so the panel has made a recommendation for using immunotherapy in combination with platinum-based chemotherapy in patients with a PD-L1 greater than 1. Again, we know that it is hard to make recommendations on what PD-L1 cutoffs are recommended in this patient population, meaning that should it be limited to patients with a PD-L1 of 1 to 4 or greater than 10? I think that the general consensus that has been gleaned from the data is that the higher the PD-L1 expression, the greater the benefit. I do want to comment on another option that is available in patients with squamous cell carcinoma compared to adenocarcinoma, and that is the combination of nivolumab and ipilimumab. Now, in CheckMate-648, nivolumab with ipilimumab was also recommended as a treatment option in patients that have a PD-L1 score of greater than 1. There was a survival benefit demonstrated with this combination compared to chemotherapy alone. And an important observation in this study is that, although there was a slightly increased rate in early death, but there was really no significant difference in PFS and OS compared to chemotherapy alone. Importantly, the treatment appeared to be pretty well tolerated by the study population. There was a notable difference in the objective response rate, which was 35% in the nivolumab plus ipilimumab group compared to patients receiving nivolumab and chemotherapy, where it was 53%. So superiority is, so the importance of chemotherapy in patients with esophageal squamous cell carcinoma is to be noted. However, there is no difference in overall survival and progression-free survival when using the combination of nivolumab and ipilimumab, and thus it affords a chemotherapy-free option for this patient population with esophageal squamous cell carcinoma and a CPS with a score of greater than 1. Brittany Harvey: Understood. I appreciate you reviewing the evidence underpinning those recommendations as well. So then the next patient population that the guideline panel addressed, what first-line therapy is recommended for patients with deficient mismatch repair, microsatellite instability-high, gastroesophageal adenocarcinoma or esophageal squamous cell carcinoma? Dr. Lakshmi Rajdev: The rate of MSI-high expression is about 3% to 7% across different studies. Now, the KEYNOTE-158 was a tumor-agnostic study in patients with non-colorectal cancers, and again, the problem with the MSI-high population, given that it is so rare, the numbers in the individual studies are fairly small. But consistent outcomes do emerge, indicating high response to immunotherapy. So in KEYNOTE-158, a response rate of about 46% was noted. The number of patients was small, it was about 24. In CheckMate-649, which is a study of chemotherapy plus or minus nivolumab in patients with advanced gastric adenocarcinoma, there was again a very small number of patients, and patients that were MSI-high or deficient MMR did experience substantial benefits with the addition of immunotherapy, with hazard ratios in the order of about 0.38. In KEYNOTE-062, again, it was a very small number of patients, again about 6% or so, and similar to CheckMate-649, a substantial benefit was noted in combination with chemotherapy, but also there were benefits noted with pembrolizumab alone. The RATIONALE-305 again was a study of tislelizumab in combination with chemotherapy and similarly showed benefits to the combination of chemotherapy plus immunotherapy in this patient population. I think that we are all aware of the dramatic benefits of immunotherapy in this particular subset of patients, deficient MMR MSI-high, and also we have seen in CheckMate-649 they did have a subset of patients that received nivolumab and ipilimumab. And in this patient population, they noted unstratified hazard ratio of 0.28. So I think that the overall consensus is that immunotherapy is a very important treatment modality in patients with deficient MMR MSI-high disease, given that a lot of the trials in gastroesophageal adenocarcinoma have utilized chemotherapy-based options, that is certainly a recommendation of the panel to use chemotherapy in combination with immunotherapy. However, on a case-by-case basis, the panel recommended immunotherapy alone as well, and given the high response rates noted in trials across different diseases as well as noted in this disease as well. Brittany Harvey: Certainly. And I appreciate you both for reviewing these first-line recommendations. So moving to later lines of therapy, Dr. Rajdev, what recommendations did the expert panel make for second or third-line therapy for gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma? Dr. Lakshmi Rajdev: So, I think that the RAINBOW trial that investigated the utility of the addition of ramucirumab as second-line therapy has been around since 2014, and those results have led to the addition of ramucirumab to taxane-based therapy in the second-line setting. Based on the utilization of oxaliplatin and platinum-based therapy in the front-line setting, there may be patients that have an underlying neuropathy, and so we wanted to really include treatment options for this patient population so that an agent that is less neurotoxic could also be recommended in combination with ramucirumab. The RAMIRIS trial is one such trial where ramucirumab was combined with FOLFIRI, and it demonstrated benefit in combination with ramucirumab. So we have listed that as a potential treatment option for patients in the second-line setting who may have an underlying neuropathy or even for whatever reason that based on the toxicity profile, that needs to be the preferred option by a physician, that recommendation is new from the older guidelines that we have. With regard to the utility of PD-1 inhibitors, there really has been no benefit noted in the second-line setting with regard to overall survival or progression-free survival, so no recommendation is made for that option. I think an important study that has been recently presented is the DESTINY-Gastric04 trial, which really has been practice-changing and has led to the recommendation for trastuzumab deruxtecan in patients that have HER2-positive metastatic gastric or GE junction adenocarcinoma. Now, this is a phase III trial in patients who retained HER2-positive disease after progressing on front-line trastuzumab-based treatments, and the comparator for this trial was trastuzumab deruxtecan versus ramucirumab plus paclitaxel. There was significant improvement and progression-free survival in patients that received trastuzumab deruxtecan. The patients that were excluded from the trial are patients that have pulmonary problems, interstitial lung disease; that is one of the toxicities of this particular agent, and close monitoring and prompt initiation of therapy such as glucocorticoid treatment in patients who develop this toxicity was also highlighted by the panel. So to summarize, the new guidelines highlight the possibility of FOLFIRI plus ramucirumab as a second-line option and then trastuzumab deruxtecan as a later-line option in patients that still retain HER2 expression. And that is very important because the trial did retest patients whether they expressed HER2. As we know, in a substantial number of patients, there is downregulation of HER2, and there is emerging data that the benefit for subsequent HER2-directed therapies is best noted in patients that still retain HER2 expression. Brittany Harvey: Great. So as our listeners have heard, there are many recommendations and new treatment options for advanced gastroesophageal cancer. Dr. Shah, earlier you highlighted the importance of biomarker testing, but I would like to hear in your view, what is the importance of this guideline and how will it impact both clinicians and patients with gastroesophageal carcinoma? Dr. Manish Shah: So as we have discussed throughout this podcast, the treatment for gastroesophageal cancer, both adenocarcinoma and squamous cell cancer, is increasingly complex, increasingly biomarker-driven. And I think the value of the guideline is to place all of that into context. So it provides the data for why certain biomarkers are important, what therapies should be indicated. Not only that, but if you are able to review the guideline, it provides the details of each of these studies and summarizes them in a meta-analysis fashion to sort of give you the context, because sometimes the individual studies can be maybe a little bit discordant or confusing and the guideline attempts to harmonize all that. And then also, I think the tables are very, very interesting because they give you actual numbers in terms of how many patients over a thousand would this benefit or how many patients over a thousand would this cause harm in terms of nausea, vomiting, or other things like that. So it gives you context for helping clinicians and patients weigh the potential benefits of the novel treatment strategies against the potential adverse events. And then finally, the guideline does also provide an algorithm that you are able to follow based on the biomarkers, and those are in figures 4 and 5. So I think overall, it is a very comprehensive guideline. It intends to make more manageable a very complex subject, and you know, I really encourage our listeners to review it after listening to the podcast. Dr. Lakshmi Rajdev: If I can add to that, I think that what is also really good about the guidelines is there are quick summaries. So if someone is busy in the clinic, of course, there is the opportunity to review the data supporting the guidelines in great depth in the manuscript, but what is also really good is that there are good summaries. In the event that you are very busy, you can easily identify what the recommendations should be for that particular patient based on these summaries. Brittany Harvey: Absolutely. Listeners are encouraged to review the full guideline, including those tables and figures that may be more helpful when they are looking for something quick to look at in the clinic as well. So, as you both mentioned, there have been a number of recent practice-changing trials in this area. So I imagine there is still a lot of ongoing research as well. So Dr. Shah, what are the outstanding questions regarding treatment options for patients with locally advanced unresectable, advanced, or metastatic gastroesophageal carcinoma? Dr. Manish Shah: I think we touched upon it a little bit. The guidelines are based on the data available, and they are primarily examining one novel therapy with chemotherapy in a specific biomarker population. But as you know, the biomarkers are not either/or; you are not either CLDN18.2 positive or PD-L1 positive. A portion of patients could have dual biomarkers, and you know, I think that we are generating data on how to manage those patients. At the recent GI Symposium in January this year, the ILUSTRO trial was presented by Dr. Shitara, which looked at combining zolbetuximab and chemotherapy with immunotherapy for dual-positive biomarkers, and that is leading to a phase III study that has begun to enroll. So unanswered questions are: how do we manage dual-positive biomarkers? The other thing that was mentioned is that the current data for mismatch repair deficiency involve chemotherapy plus immunotherapy. Only squamous cell cancer is there a study with a positive non-chemotherapy kind of backbone, that is CheckMate-648 that Dr. Rajdev mentioned. As we move forward, it will be good to get data on non-chemotherapy options in certain biomarker-positive populations. And then finally, another update, which is likely to be practice-changing, is the HERIZON-GEA-01 study that looked at zanidatamab, which is another biparatopic antibody that targets HER2, and that is likely to change practice. And as that data gets published, we may look to even do a rapid update for the current immunotherapy and targeted therapy guideline that is just being published. Dr. Lakshmi Rajdev: So, if I can add to that, there are numerous ADCs that look very interesting. There are bispecific antibodies; in fact, the zanidatamab is a bispecific antibody showing improved activity in patients with HER2-positive disease. So I think there are studies from Asia looking at CLDN CAR T-based therapies. So, I think that there are a lot of novel agents and a lot of excitement in the field. We know that the bemarituzumab study, unfortunately, the FGFR2 inhibitor failed to demonstrate any benefit, but I think that there are other agents that are being explored, so there are newer targets, newer agents, ADCs, bispecifics that could potentially change the field in the future. Brittany Harvey: Yes, we will look forward to the data to address these unanswered questions and new agents and inform future guideline updates. So, I would like to thank you both for all of your work to review the evidence here and update this important guideline, and for your time today, Dr. Rajdev and Dr. Shah. Dr. Lakshmi Rajdev: Thank you. Dr. Manish Shah: 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/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 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.
From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.In this episode, Dr Matulonis sat down with guest Susana M. Campos, MD, MPH. Dr Campos is the clinical director and director of Educational Initiatives for the of the Division of Gynecologic Oncology at Dana-Farber Cancer Institute, and an institute physician and assistant professor of medicine at Harvard Medical School in Boston, Massachusetts. Drs Matulonis and Campos discussed the evolving landscape of newly diagnosed cervical cancer, from epidemiologic trends to emerging therapeutic strategies.According to 2026 estimates from the American Cancer Society, approximately 13,400 new cases of invasive cervical cancer will be diagnosed in the United States, with roughly 4200 deaths. Although incidence has declined over time due to human papillomavirus (HPV) vaccination and screening efforts, rates have plateaued, and the disease burden remains substantial, particularly among women aged 35 to 64 years. Dr Campos noted that approximately half of cases occur in women younger than 50 years of age, and about 20% are diagnosed in women older than 65 years of age.Dr Campos reviewed common presenting symptoms, including abnormal vaginal bleeding, intermenstrual or postmenopausal bleeding, abnormal discharge, pelvic pain, and, in advanced cases, urinary symptoms or leg swelling. She explained that diagnosis begins with pelvic examination and cervical cytology or HPV testing, followed by colposcopy and biopsy when indicated. Although cervical cancer remains one of the few malignancies that is clinically staged, imaging modalities, such as MRI, CT, and PET scans, are critical to accurately defining disease extent, they underscored. Moreover, the discussion highlighted transformative advances in locally advanced disease. The phase 3 KEYNOTE-A18 trial (NCT04221945) demonstrated improved progression-free and overall survival with the addition of pembrolizumab (Keytruda) to standard chemoradiation, establishing a new standard for high-risk patients, Campos stated. Similarly, the phase 3 INTERLACE trial (NCT01566240) showed that short-course induction chemotherapy with carboplatin and paclitaxel before chemoradiation improved long-term outcomes. Campos forecasted that ongoing studies, including the phase 3 NRG-GY037 trial (NCT07061977), may integrate these approaches and further refine optimal treatment sequencing.Lastly, Drs Matulonis and Campos highlighted the expanding therapeutic arsenal in the recurrent and metastatic setting. Campos noted how antibody-drug conjugates, such as tisotumab vedotin-tftv (Tivdak) and fam-trastuzumab deruxtecan-nxki (Enhertu), have demonstrated meaningful activity, particularly in biomarker-selected populations. Campos added that investigational strategies targeting TROP2, such as sacituzumab govitecan-hziy (Trodelvy), represent additional promising avenues.Despite these advances, both experts emphasized that prevention remains paramount. Widespread uptake of HPV vaccination, including the 9-valent vaccine, as well as adherence to routine cervical screening, are essential to reducing the long-term burden of this largely preventable disease.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.
Sarah Poland, MD, lead author of a recently published article in the journal ONCOLOGY titled Advances in Immunotherapy for Breast Cancer, highlighted key findings from her review in a conversation with CancerNetwork®.1 Throughout the discussion, she spoke about: Shifting Perspectives on Immunogenicity: Historically, breast cancer was considered a “cold,” poorly immunogenic tumor due to low tumor mutational burden (TMB) and few tumor-infiltrating lymphocytes (TILs). Poland highlighted how clinical research has shifted this perspective, particularly through the study of triple-negative breast cancer (TNBC), which often exhibits higher PD-L1 expression and immune infiltration.Key Clinical Milestones: The review highlighted foundational data that established immunotherapy as a standard of care: Early-Stage TNBC: The phase 3 KEYNOTE-522 trial (NCT03036488) established pembrolizumab (Keytruda) plus chemotherapy as a standard neoadjuvant treatment for stage II to III TNBC.2 Metastatic TNBC: The phase 3 KEYNOTE-355 trial (NCT02819518) demonstrated the benefit of pembrolizumab in PD-L1–positive metastatic disease.3 Managing Toxicity and Rechallenge: Poland addressed the feasibility of pembrolizumab rechallenge after an immune-related adverse effect (irAE), emphasizing that while possible, it requires a highly individualized approach based on the severity and timing of the initial toxicity.The Future Landscape: Beyond PD-1/PD-L1 inhibitors, the discussion covered emerging technologies that are poised to redefine treatment: Antibody-Drug Conjugates (ADCs): Exploration of novel combinations of ADCs with immunotherapy. Emerging Modalities: The potential role of bispecific antibodies and vaccine trials utilizing tumor antigens. Subtype Expansion: Emerging evidence supporting the efficacy of immunotherapy in hormone receptor–positive and HER2-positive subtypes, moving beyond the traditional focus on TNBC. Unmet Educational Needs: Poland emphasized the importance of resources that connect providers and patients, particularly in translating complex trial data into clinical practice and addressing patient concerns regarding the newest therapies and trials.Poland is from the Department of Medicine in the Section of Hematology/Oncology at The University of Chicago.References1. Poland S, de Oliveira Andrade M, Nanda R. Advances in immunotherapy for breast cancer. Oncology (Williston Park). 2026;40(1):8-15. doi:10.46883/2026.259210612. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa19105493. Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217-226. doi:10.1056/NEJMoa2202809
In this episode of Careers in Discovery, Tyler is joined by Marc Damelin, Chief Scientific Officer at Alphina Therapeutics. Marc shares his journey from physics undergraduate to Biotech leader, and how a love of problem‑solving gradually drew him from yeast genetics into human disease and ultimately into drug development. After a decade in big pharma working on antibody–drug conjugates, he steps into Biotech leadership, first at Mersana and now at Alphina, where he's pioneering a new class of ADCs built around NAMPT inhibition. Along the way, Marc reflects on choosing industry without having a clear plan, understanding what makes a role the right fit, and why being truly data‑driven is one of the most important habits a scientist can develop. An open, forward‑looking conversation about evidence, judgment and the momentum that comes from backing the right ideas at the right time.
In this episode of Denatured, Jennifer C. Smith-Parker speaks with Dr. Rob Monroe, Vice President and Chief Scientific Officer of Oncology at Danaher Corporation and Chief Medical Officer at Leica Biosystems, and Jennifer Fakish, Vice President and Franchise Head of Oncology at Danaher Corporation. We'll be discussing how antibody drug conjugates (ADCs) are transforming cancer care and with AI-powered pathology, doctors can now measure her HER2 more precisely to match patients with the best treatments. HostJennifer Smith-Parker, Director of Insights, BioSpaceGuestsDr. Rob Monroe, Vice President and Chief Scientific Officer, Oncology, Danaher Corporation; Chief Medical Officer, Leica BiosystemsJennifer Faikish, Vice President and Franchise Head, Oncology, Danaher CorporationDisclaimer: The views expressed in this discussion by guests are their own and do not represent those of their organizations.
You're using Active Directory Certificate Services - but is it configured securely? Richard talks to Ron Arestia about his work with organizations implementing their own Public Key Infrastructure (PKI) with ADCS. Ron explains how poorly configured ADCS enables lateral attacks within an organization once an initial breach occurs, allowing black hats to move throughout your network. A well-designed PKI system has tiers of protection, with the top level completely disconnected from the network. Or do you really need your own PKI system? The conversation digs into the various scenarios, including third-party options. Certificates are the top level of security for your organization - you need to get it right!LinksActive Directory Certificate ServicesWindows Hello for BusinessCertified Pre-OwnedMicrosoft Defender for IdentitySecure Privileged AccessPass the HashMicrosoft Cloud PKI for Microsoft IntuneMicrosoft Entra Conditional AccessMicrosoft AutopilotRon's BlogRecorded February 6, 2026
Featuring an interview with Dr Kathleen N Moore, including the following topics: Overview of the mechanism of action and pharmacology of antibody-drug conjugates (ADCs) (0:00) Comparing toxicities of conventional chemotherapy and ADCs (6:26) Potential of ADCs as maintenance therapy for ovarian cancer (11:35) Treatment based on platinum sensitivity and homologous recombination-deficiency status (15:10) Case: A woman in her mid 70s presenting with Stage IV ovarian cancer receives raludotatug deruxtecan (18:46) Case: A woman in her mid 60s with relapsed/refractory ovarian cancer receives mirvetuximab soravtansine (41:22) Case: A woman in her early 70s with relapsed/refractory ovarian cancer receives multiple ADCs in clinical trials (45:57) CME information and select publications
Featuring a slide presentation and related discussion from Dr Kathleen N Moore, including the following topics: Overview of developments and opportunities with antibody-drug conjugates (ADCs) in ovarian cancer(0:00) Targeting folate receptor alpha with mirvetuximab soravtansine (3:59) Targeting TROP2 with ADCs (9:12) Targeting folate receptor alpha with ADCs (14:17) Targeting cadherin-6 with ADCs (17:27) Targeting HER2 with ADCs (26:12) Potential of ADCs in the treatment of platinum-sensitive ovarian cancer (28:38) CME information and select publications
Dr. Sonam Puri discusses the full update to the living guideline on stage IV NSCLC with driver alterations. She shares a new overarching recommendation on biomarking testing and explains the new recommendations and the supporting evidence for first-line and subsequent therapies for patients with stage IV NSCLC and driver alterations including EGFR, MET, ROS1, and HER2. Dr. Puri talks about the importance of this guideline and rapidly evolving areas of research that will impact future updates. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.0" 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-25-02822 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. Sonam Puri from Moffitt Cancer Center, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO Living Guideline, Version 2026.3.0." It's great to have you here today, Dr. Puri. Dr. Sonam Puri: Thanks, Brittany. 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. Puri, 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 that we're here today to talk about, Dr. Puri, 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 data prompted this latest update to the recommendations? Dr. Sonam Puri: So Brittany, non-small cell lung cancer is one of the fastest-moving areas in oncology right now, particularly when it comes to targeted therapy for driver alterations. New data are emerging continuously from clinical trials, regulatory approvals, real-world experience, which is exactly why these are living guidelines. The goal is to rapidly integrate important advances as they happen, rather than waiting for years for a traditional update. Since the last full update of the ASCO Stage IV Non-small Cell Lung Cancer Guideline with Driver Alterations published in 2024, there have been seven new regulatory approvals and changes in first-line therapy for some driver alterations. [This version] of the "Stage IV Non-small Cell Lung Cancer Guidelines with Driver Alterations" represents a full update, which means that the panel reviewed and refreshed every applicable section of the guideline to reflect the most current evidence across therapies including sequencing and clinical decision-making. This is to ensure that clinicians have up-to-date practical guidelines that keep pace with how quickly the field is evolving. Brittany Harvey: Absolutely. As you mentioned, this is a very fast-moving space and this full update helps condense all of those versions that the panel reviewed before into one document, along with additional approvals and new trials that you reviewed during this time period. So then, the first aspect of the guideline is there's a new overarching recommendation on biomarker testing. Could you speak a little bit to that updated recommendation? Dr. Sonam Puri: Yeah, definitely. So the panel has discussed and provided recommendations on comprehensive biomarker testing and its importance in all patients diagnosed with non-small cell lung cancer. Ideally, biomarker testing should include a broad-based next-generation sequencing panel, rather than single-gene tests, along with immunohistochemistry for important markers such as PD-L1, HER2, and MET. These results really drive treatment decisions, both in frontline settings for all patients diagnosed with non-small cell lung cancer and in subsequent line settings for patients with non-small cell lung cancer harboring certain targetable alterations. Specifically in the frontline setting, it helps determine whether a patient should receive upfront targeted therapy or immunotherapy-based approach. We now have strong data that shows that complete molecular profiling results before starting first-line therapy is associated with better overall survival and actually more cost-effective care. Using both tissue and blood-based testing can improve likelihood of getting actionable results in a timely way, and we've also provided guidance on platforms that include RNA sequencing, which are specifically helpful for identifying gene fusions that might be otherwise missed with other platforms. On the flip side, outside of a truly resource-limited setting, single-gene PCR testing really should not be routine anymore. This is what the panel recommends. It's less sensitive and inefficient and increases the risk of missing important actionable alterations. Brittany Harvey: Understood. I appreciate you reviewing that recommendation. It really helps identify critical individual factors to match the best treatment option to each individual patient. So then, following that recommendation, what are the updated recommendations on first-line therapy for patients with stage IV non-small cell lung cancer with a driver alteration? Dr. Sonam Puri: Since the last full update in 2024, there have been four additional interim updates which were published across 2024 and 2025. Compared to the last version, there have been several updates which have been included in this full update. One of the most important shifts has been in first-line treatment of patients with non-small cell lung cancer harboring the classical, or what we call as typical, EGFR mutation. The current version of the recommendation is based on the updated survival data from the phase III FLAURA2 and MARIPOSA studies, based on which the panel recommended to offer either osimertinib combined with platinum-pemetrexed chemotherapy or the combination of amivantamab plus lazertinib in the first-line treatment of classical EGFR mutations. And these recommendations, as I mentioned, are grounded in the results of the FLAURA2 and MARIPOSA trials, both of which demonstrated improvement in progression-free survival and overall survival compared to osimertinib alone in patients with common EGFR mutations. That being said, the panel actually spent significant time discussing the toxicities associated with these treatments as well. These combination approaches come with higher toxicity, longer infusion time, increased treatment frequency. So while combination therapy is now recommended as preferred, the panel has recommended that osimertinib monotherapy remains a reasonable option, particularly for patients with poor performance status and for those who are not interested in treatment intensification after knowing the risks and benefits. Brittany Harvey: Absolutely. It's important to consider both those benefits and risks of those adverse events that you mentioned to match appropriately individualized patient care. So then, beyond those recommendations for first-line therapy, what is new for second-line and subsequent therapies? Dr. Sonam Puri: So this is a section that saw several major updates, particularly again in the EGFR space. The first was an update on treatment after progression on osimertinib for patients with classical EGFR mutation. Here the panel recommends the combination of amivantamab plus chemotherapy, and this recommendation was based on the phase III MARIPOSA-2 trial, which compared amivantamab plus chemotherapy with chemotherapy alone with progression-free survival as the primary endpoint. The study met its primary endpoint, showing an improvement in median PFS with the combination of amivantamab plus chemotherapy compared to chemotherapy alone. And as expected, the combination was associated with higher toxicity. So, although the panel recommends this regimen, the panel emphasizes that patients should be counseled on the side effects which may be moderate to severe with the combination therapy approach. In addition, a new recommendation was added for patients who are not candidates for amivantamab plus chemotherapy. In those cases, platinum-based chemotherapy with or without continuation of osimertinib may be offered, and the option of continuing osimertinib with chemotherapy was recommended and supported by data from a recently presented phase III COMPEL study, which randomized 98 patients with EGFR exon 19 deletion or L858R-mutated advanced non-small cell lung cancer who had experienced no CNS progression on first-line osimertinib, and these patients were randomized to receive platinum-pemetrexed chemotherapy with osimertinib or placebo. Although this study was small, it demonstrated a PFS benefit with continuation of osimertinib with chemotherapy, and this approach may be appropriate for patients without CNS progression who prefer or require alternatives to more intensive treatment strategies. Next was an update on options for patients with EGFR-mutated lung cancer after progression on osimertinib and platinum-based chemotherapy. Here the panel recommended that for patients whose disease has progressed after both osimertinib and platinum-based chemotherapy, a new drug known as datopotamab deruxtecan can be offered as a treatment option. And this treatment recommendation was based on evaluation of pooled data from the TROPION-Lung01 and TROPION-Lung05 study, in which in the pooled analysis about 114 patients with EGFR-mutant non-small cell lung cancer were treated with Dato-DXd, 57% of whom had received three or more prior lines of treatment, and what was observed was an overall response rate of 45% with a median duration of response of 6.5 months. So definitely promising results. Next, we focused on updates to subsequent therapy options for patients with another type of EGFR mutation known as EGFR exon 20 insertion mutations. In this section, the panel added sunvozertinib as a subsequent line option after progression on platinum-based chemotherapy with or without amivantamab. Sunvozertinib is an oral, irreversible, and selective EGFR tyrosine kinase inhibitor with efficacy demonstrated in the phase II WU-KONG6 study conducted in Chinese patient population. In this study, amongst 104 patients with platinum-pretreated EGFR exon 20 mutated non-small cell lung cancer, the observed response rate was 61%. Staying in the EGFR space, the panel added a recommendation for patients with acquired MET amplification following progression on EGFR TKI therapy. In these situations, the panel recommended that treatment may be offered with osimertinib in combination with either tepotinib or savolitinib. As our listeners may know, MET amplification occurs in approximately 10% to 15% of patients with EGFR-mutated non-small cell lung cancer when they progress on third-generation EGFR TKIs, and detection of MET amplification is done with various methods, such as tissue-based methods like FISH, NGS, and IHC, as well as ctDNA-based NGS with variable cut-offs. Over the last few years, several studies have informed this recommendation. I'm going to be discussing some of them. In the phase II ORCHARD trial, 32 patients with MET-amplified non-small cell lung cancer after progression on first-line osimertinib were evaluated, where the combination of osimertinib plus savolitinib achieved an overall response rate of 47% with a duration of response of 14.5 months. More recently, the phase II SAVANNAH trial reported outcomes in 80 patients with MET-amplified tumors after progression on osimertinib, and in this patient population, the combination of savolitinib and osimertinib achieved an overall response rate of 56% with a median PFS of 7.4 months. And lastly, the phase II single-arm INSIGHT 2 trial assessed the efficacy of osimertinib plus tepotinib in patients with advanced EGFR-mutant non-small cell lung cancer who had disease progression following first-line osimertinib therapy. And in this study, in a cohort of 98 patients with MET-amplified tumors confirmed by central testing, the overall response rate with the combination was 50% with a duration of response of 8.5 months. So definitely informing this guideline recommendation. Next, we had an update on recommendation in patients with ROS1-rearranged non-small cell lung cancer. For patients with ROS1-rearranged non-small cell lung cancer, the panel recommended specifically for patients who progressed after first-line ROS1 TKIs, the addition of taletrectinib as a new option alongside repotrectinib. And this recommendation was based on analysis of the results of the TRUST-I and TRUST-II studies, which showed that amongst 113 tyrosine kinase inhibitor-pretreated patients, taletrectinib achieved a confirmed overall response rate of 55.8% with a median duration of response of 16.6 months and a median PFS of 9.7 months, a very promising agent. Finally, for patients with HER2 exon 20 mutated non-small cell lung cancer, the panel added two new oral HER2 tyrosine kinase inhibitors, zongertinib and sevabertinib, as options in addition to T-DXd and after exposure to T-DXd. These recommendations are based on early phase data from two trials: the phase I Beamion LUNG-01 study, which evaluated zongertinib, and the phase I/II SOHO-01 study that evaluated sevabertinib. In this study, zongertinib demonstrated an overall response rate of 71% in previously treated patients, with an overall response rate of 48% amongst patients who had received prior HER2-directed ADCs including T-DXd. Sevabertinib in its early phase study showed an overall response rate of 64% in previously treated but HER2 therapy-naive patients, and an overall response rate of 38% in patients previously exposed to HER2-directed therapy. The panel believes that both agents had manageable toxicity profile and represent meaningful new options for this patient population. Brittany Harvey: Certainly, it's an active space of research, and I appreciate you reviewing the evidence underpinning all of these recommendations for our listeners. So, it's great to have these new options for patients in the later-line settings. And given all of these updates in both the first and the later-line settings, what should clinicians know as they implement this latest living guideline update, and how do these changes impact patients with non-small cell lung cancer? Dr. Sonam Puri: Some great questions, Brittany. I think for clinicians when implementing this update, I think about two practical steps. First is reiterating the importance of comprehensive biomarker testing. That is the only way to identify key drivers and resistance mechanisms that we are now targeting. And second, picking a first-line strategy that balances efficacy and toxicity and patient preference for your specific patient. I think informed decision-making, shared decision-making is more important than any time right now. It has always been important, but definitely very important now. For patients, this guideline brings recommendations on more personalized treatment options for both first-line and post-progression settings, which potentially means better outcomes. But it is also very important for our patients to continue to have informed conversations about side effects, time commitment, and what matters most to them with their providers. The panel in this version of the guideline specifically acknowledges the real-world barriers that prevent patients from receiving guideline-concordant therapy, including challenges with access to comprehensive molecular testing and treatment availability, and the panel emphasizes on the importance of shared decision-making, and we provide practical discussion points to help clinicians navigate these conversations with the patient. In addition, the panel has also addressed common real-world clinical complexities, such as treating elderly or frail patients, managing multiple chronic conditions, considerations around pregnancy and fertility, and certain disease scenarios such as oligoprogression or oligometastatic disease. And where available, the guideline summarizes this existing data to support informed individual decision-making in these complex situations. Brittany Harvey: Shared decision-making is really paramount, especially with all of the options and weighing the risks and benefits and considering the individual circumstances of each patient that comes before a clinician. We've talked a lot about all of the new studies that the panel has reviewed, but what other studies or areas of research is the panel examining for future updates to this living guideline as it continues to be updated on an ongoing basis? Dr. Sonam Puri: Yes, definitely, so much to look forward to, right? Looking ahead, the panel is closely monitoring several rapidly evolving areas that are likely to shape future updates of the guideline. This includes emerging data from ongoing later-phase studies, particularly the studies that are evaluating these new targeted agents moving to earlier lines of therapy, alongside studies evaluating additional combination strategies or more refined approaches to treatment sequencing. We're also closely watching advances in biomarker testing, the evolving understanding of resistance mechanisms, development of new targets, and promising therapeutic agents. I think ultimately the living guideline exists to help clinicians and patients navigate this rapidly evolving field, and we would like to ensure that scientific advances are rapidly translated into better, more personalized patient care. Brittany Harvey: Definitely. We'll look forward to those updates from those ongoing trials and future areas of research that you mentioned to provide better options for patients with non-small cell lung cancer and a driver alteration. So I want to thank you so much for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Puri. Dr. Sonam Puri: Thanks so much. Thanks so much for the opportunity. 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 available in the Apple App Store or the Google Play Store. There's also a companion episode with Dr. Reuss on the related living guideline on stage IV non-small cell lung cancer without driver alterations that listeners can find in their feeds as well. And 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.
Please visit answersincme.com/860/29264-replay to participate, download slides and supporting materials, complete the post test, and get a certificate. Presented by Aditya Bardia, MD and Tiffany A. Traina, MD, FASCO. In this activity, experts in breast cancer share evidence-based insights on integrating current and emerging TROP2-directed antibody-drug conjugates (ADCs) into real-world triple-negative breast cancer (TNBC) care. Upon completion of this activity, participants should be better able to: Identify the role of TROP2-directed antibody-drug conjugates (ADCs) in metastatic triple-negative breast cancer (TNBC) treatment; Compare the latest clinical data on available and emerging TROP2-targeting ADCs for the first-line treatment of patients with TNBC; and Discuss evidence-based strategies to optimize the selection of appropriate patients for first-line treatment with TROP2-targeting ADCs.
Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Let's dive into the latest happenings in this dynamic industry.Starting with a look at the projected launch of top drugs anticipated in 2026, it's fascinating to see how these developments are poised to influence the market. These drugs could collectively generate a substantial $45.9 billion in annual sales by 2032, underscoring their economic impact and potential to address unmet medical needs. This reflects a robust pipeline of innovative treatments, marking significant therapeutic advancements on the horizon.Regulatory actions continue to be a pivotal force in shaping market dynamics. The FDA's recent issuance of complete response letters to Aquestive Therapeutics and Pharming resulted in contrasting market reactions, with Aquestive's shares rising while Pharming's declined. This scenario highlights the critical role of regulatory decisions in shaping company fortunes and investor confidence. Additionally, the FDA has introduced a precheck manufacturing program aimed at streamlining domestic drug production processes. This initiative is part of a broader trend to bolster U.S. pharmaceutical manufacturing capabilities amid global supply chain concerns, reflecting an effort to reduce complexities associated with setting up manufacturing plants domestically.In the realm of policy debates, there's notable discord among Trump administration officials over the future of COVID-19 vaccines in the U.S. market. This internal division could have far-reaching implications for public health strategies and vaccine accessibility, emphasizing ongoing challenges in pandemic management and policy alignment.Turning to scientific innovation, Daiichi Sankyo's development of antibody-drug conjugates (ADCs) has faced some setbacks. The company has discontinued an internal next-wave candidate and is experiencing delays in pivotal phase 3 trial readouts for its AstraZeneca-partnered candidate, Datroway. Despite these challenges, ADCs remain a promising area of oncology research due to their targeted therapeutic potential.Positive regulatory feedback from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has provided a boost for companies like Novo Nordisk and Amgen. Novo Nordisk received approval for semaglutide for non-alcoholic steatohepatitis (NASH), highlighting its potential to address this liver disease with limited treatment options. Conversely, Amgen's Tavneos faces a re-review due to data integrity concerns, illustrating the rigorous scrutiny that accompanies pharmaceutical approvals and the importance of maintaining data integrity throughout development.Sanofi's pipeline reflects mixed outcomes as its GCS inhibitor failed a phase 3 trial for Fabry disease but showed promise in Gaucher disease. This underscores the inherent uncertainties and challenges faced in drug development, where promising candidates may not always meet clinical expectations.In broader scientific research, AstraZeneca identified 22 genes potentially linked to chronic diseases following Epstein-Barr virus infection. This finding advances our understanding of viral pathogenesis and its long-term health impacts, potentially guiding future therapeutic interventions.These developments illustrate a dynamic landscape where scientific innovation, regulatory oversight, and market forces converge to shape the future of healthcare. Breakthrough technologies and new therapeutic approaches hold promise for improving patient care and advancing drug development. However, navigating complex regulatory environments and addressing data integrity concerns remain critical challenges that companies must overcome to bring these innovations to market successfully.On another front, Roche's substantial $1.7 billion deal with Sanegene marks its re-engageSupport the show
In today's episode, the discussion features Komal Jhaveri, MD, FACP, a breast medical oncologist at Memorial Sloan Kettering Cancer Center, who reviewed the evolving role of TROP2-directed antibody–drug conjugates (ADCs) in the management of hormone receptor (HR)–positive, HER2-negative metastatic breast cancer. She drew on findings from the phase 3 ASCENT-07 trial (NCT05840211), which evaluated sacituzumab govitecan-hziy (Trodelvy) in the first-line setting following endocrine therapy for patients with HR-positive, HER2-negative metastatic breast cancer.In this exclusive interview, Dr Jhaveri discussed the rationale for evaluating sacituzumab govitecan earlier in the treatment paradigm, summarized key efficacy outcomes from ASCENT-07, and contextualized why the trial did not meet its primary progression-free survival end point. She also highlighted how disease biology and patient selection may influence outcomes when ADCs are moved into earlier lines of therapy, and outlined practical considerations for toxicity management and future trial design as the TROP2 ADC landscape continues to evolve.asts, Spotify, and many of your other favorite podcast platforms,* so you get a notification every time a new episode is posted. While you are there, please take a moment to rate us!
In this podcast, experts Drs. Hope Rugo, Alison Conlin, Marleen Kok and Heather McArthur discuss results of recent pivotal clinical trials and their impact on current and evolving treatment paradigms for patients with metastatic triple-negative breast cancer.
CME credits: 0.25 Valid until: 30-01-2027 Claim your CME credit at https://reachmd.com/programs/cme/progress-in-breast-cancer-care-translating-sabcs-data-into-practice/48989/ This online educational activity equips clinicians with up-to-date, practice-changing insights from SABCS 2025. Experts review pivotal data across early-stage and metastatic breast cancer, including advances in HER2- and TROP2-directed ADCs, and discuss how these findings can meaningfully inform treatment selection. Participants will learn how to apply new evidence to expand therapeutic options, improve patient outcomes, and navigate emerging safety and quality of life considerations.=
In episode #97 of “The Weekly Bioanalysis” podcast, John and Dom focus on a review of 2025 drug approvals, revealing a surprisingly strong year for small molecules despite long-standing predictions of their decline. Of the 53 FDA approvals, 31 were small molecules, with additional complexity coming from ADCs and RNAi therapies, underscoring the continued importance of small-molecule development and analytics. The hosts also compare U.S. and European approvals, noting meaningful differences driven by regulatory timing and regional priorities rather than scientific divergence. They highlight encouraging momentum in ADCs, the role of acquisitions in successful approvals, and a broad mix of indications—from rare diseases and oncology to neurology and vaccines. Overall, the episode reinforces that innovation remains diverse, with small molecules, large molecules, and conjugated technologies all playing critical roles in modern drug development. If you want a comprehensive view of the noteworthy approvals from 2025, this is the episode you're looking for!“The Weekly Bioanalysis” is a podcast dedicated to discussing bioanalytical news, tools and services related to the pharmaceutical, biopharmaceutical and biomarker industries. Every month, KCAS Bio will bring you another 60 minutes (or so) of friendly banter between our two finest Senior Scientific Advisors as they chat over coffee and discuss what they've learned about the bioanalytical world the past couple of weeks. “The Weekly Bioanalysis” is brought to you by KCAS Bio.KCAS Bio is a progressive growing contract research organization of well over 250 talented and dedicated individuals with growing operations in Kansas City, Doylestown, PA, and Lyon, France, where we are committed to serving our clients and improving health worldwide. Our experienced scientists provide stand-alone bioanalytical services to the pharmaceutical, biopharmaceutical, animal health and medical device industries.
Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we'll delve into the multitude of changes and advancements sweeping across the industry, each with profound implications for drug development, patient care, and market dynamics.The pharmaceutical landscape continues to transform as companies like Daiichi Sankyo make significant progress with antibody-drug conjugates (ADCs). Their collaboration with AstraZeneca on products like Enhertu and Datroway represents a robust push into earlier lines of therapy. This strategic move aligns with a broader industry trend where ADCs are being positioned as front-line oncology treatments. These therapies are lauded for their targeted delivery mechanisms that maximize therapeutic efficacy while minimizing off-target effects. However, the competitive landscape is becoming increasingly fierce, necessitating robust clinical data to stand out in this rapidly evolving market segment.Elsewhere, Moderna's recent decision to pause new late-stage trials for infectious disease vaccines highlights the intricate interplay between public sentiment and corporate strategy. The rising anti-vaccine sentiment in the U.S., compounded by diminishing support infrastructure from previous administrations, has significantly influenced Moderna's strategic recalibration. This situation underscores a critical challenge for developers of mRNA platforms: how to navigate complex public perceptions and policy landscapes while pushing forward with vaccine innovations.From a regulatory perspective, Recipharm's commissioning of a new facility in Bengaluru, India for non-bacterial beta-lactam drugs aligns with evolving FDA standards. This investment is not just about compliance; it's a proactive adaptation to meet rising customer demand and represents a strategic partnership with a major biopharmaceutical player. Such collaborations are crucial as they help scale drug production capabilities effectively.The dissolution of the marketing partnership between Arcutis and Kowa over Zoryve reflects the ever-dynamic nature of commercial collaborations within the industry. Originally intended to broaden Zoryve's market beyond dermatologists to include primary care physicians, this shift may indicate strategic realignments or divergent priorities between partners. Such changes can significantly impact market penetration strategies and highlight the importance of aligned goals within partnerships.In Europe, regulatory expansion by GSK of its Arexvy vaccine for all adults marks a pivotal milestone in widening access to crucial vaccines. This development not only enhances GSK's market presence but also underscores the agility required in regulatory responses to public health needs.On the financial front, settlements under the False Claims Act reaching $6.8 billion in FY2025 demonstrate heightened scrutiny on compliance practices within the industry. This serves as a stark reminder of both financial and reputational risks tied to non-compliance and underscores an ongoing need for stringent oversight mechanisms.Amidst economic uncertainties, AstraZeneca's decision to pause its UK research site investment reflects broader industry challenges related to strategic reallocations of resources. Companies are increasingly re-evaluating their geographic footprints and investment priorities in response to evolving market conditions.In precision oncology, Guardant Health's FDA approval for its Guardant360 CDx test in conjunction with Pfizer's Braftovi highlights how companion diagnostics are becoming integral in enhancing therapeutic outcomes through tailoring treatments based on specific genetic profiles. These developments illustrate a multifaceted landscape where scientific innovation, regulatory changes, strategic partnerships, and compliance considerations converge.The recent landscapSupport the show
In this episode of the YUromigospodcast, Brian Rini, Tom Powles, and Karine Tawagi discuss the complexities of immunotherapy re-challenge in bladder cancer. They explore the current landscape, including the challenges of existing data, the importance of understanding patient responses, and the potential for future research in antibody-drug conjugates (ADCs). The conversation highlights the need for more definitive studies to guide treatment decisions and improve patient outcomes.
Do pets reach back after death? Jimmy Akin and Dom Bettinelli assess new scientific studies on animal after-death communications. Can warning apparitions, shared sightings, and sensory details offer evidence for animal life after death? The post Ghost Pets! (Animal After Death Communications, ADCs) appeared first on StarQuest Media.
Do pets reach back after death? Jimmy Akin and Dom Bettinelli assess new scientific studies on animal after-death communications. Can warning apparitions, shared sightings, and sensory details offer evidence for animal life after death?
Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Kormal Jhaveri, MD, FACP Guest: Vanessa Soto-Romano, RN There's been recent progress with antibody-drug conjugates (ADCs) for HER2-negative breast cancers,1-3 and most recently, patients with metastatic HR+ HER2- breast cancer. The phase III TROPION-Breast01 study examined the efficacy and safety of datopotamab deruxtecan-dInk (Dato-DXd) compared to investigator's choice single-agent chemotherapy, resulting in the approval of this agent in January 2025. Joining Dr. Charles Turck to discuss Dato-DXd for patients with HR-positive, HER2-negative metastatic breast cancer, data from the TROPION-Breast01 trial, and strategies for managing select adverse reactions with this therapy are Dr. Komal Jhaveri and Nurse Vanessa Soto-Romano. Dr. Jhaveri is a breast medical oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center in New York, and Nurse Soto-Romano is a Clinical Trials Nurse, also at Memorial Sloan Kettering Cancer Center in New York. Dr. Komal JhaveriConsultant/advisory board role: Novartis, Pfizer, Genentech, Eisai, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Menarini/Stemline, Gilead, Scorpion Therapeutics, Bicycle Therapeutics, Olema Pharmaceuticals, Lilly/Loxo Oncology, Merck Pharmaceuticals, Zymeworks, Halda Therapeutics, Arivinas and RayzebioResearch Funding support to the Institution: Novartis, Genentech, AstraZeneca, Pfizer, Lilly/Loxo Oncology, Zymeworks, Gilead, PUMA Biotechnology, Merck Pharmaceuticals, Scorpion Therapeutics, Rayzebio, Eisai, Bicycle Therapeutics, Bridge Bio Oncology Therapeutics, and Blueprint Medicines. Nurse Soto-RomanoConsultant/advisory board role: AstraZeneca …
Featuring perspectives from Dr Nancy L Bartlett, Dr John P Leonard, Dr Matthew Matasar, Dr Loretta J Nastoupil and Prof Pier Luigi Zinzani, including the following topics: Introduction (0:00) Rational Incorporation of Antibody-Drug Conjugates (ADCs) into the Management of Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) — Dr Matasar (1:34) Case: A man in his late 50s who presents with left testicular swelling and abdominal discomfort is diagnosed with ABC-subtype Stage IV DLBCL — Laurie H Sehn, MD, MPH (11:27) Clinical Utility of CD19-Directed Monoclonal Antibodies for DLBCL and Follicular Lymphoma (FL) — Dr Leonard (19:00) Case: A woman in her early 80s with refractory DLBCL receives tafasitamab/lenalidomide — Carla Casulo, MD (32:50) Case: A man in his late 70s with chronic renal disease and relapsed cutaneous DLBCL receives tafasitamab and dose-reduced lenalidomide — Matthew Lunning, DO (35:51) Optimal Use of ADCs in the Treatment of Relapsed/Refractory DLBCL — Prof Zinzani (42:09) Case: A woman in her late 60s with relapsed DLBCL after polatuzumab vedotin with bendamustine/rituximab receives loncastuximab tesirine with partial response and develops a rash — Dr Casulo (57:45) Case: A woman in her early 40s with multiregimen-relapsed GCB-type DLBCL experiences disease progression on loncastuximab tesirine and receives brentuximab vedotin with lenalidomide/rituximab (1:03:07) Bispecific Antibody Therapy for DLBCL — Dr Bartlett (1:08:31) Case: A man in his mid 60s with DLBCL and early relapse on axicabtagene ciloleucel receives glofitamab — Dr Sehn (1:22:33) Case: A man in his late 60s with Type 2 diabetes, congestive heart failure and COPD receives glofitamab monotherapy after glofitamab with gemcitabine/oxaliplatin for relapsed GCB-type double-hit DLBCL — Dr Lunning (1:29:06) Bispecific Antibody Therapy for FL and Other Lymphoma Subtypes — Dr Nastoupil (1:35:34) Case: A woman in her mid 50s with multiregimen-recurrent FL receives mosunetuzumab — Dr Casulo (1:47:01) Case: A man in his late 70s with multiregimen-refractory FL receives mosunetuzumab and achieves an ongoing complete response — Dr Sehn (1:52:23) CME information and select publications
Esportmaníacos 2456: ¡Hoy han arrancado las ligas! LPL y LCK han tenido su día inaugural y hemos hablado de las primeras impresiones de la temporada ahora que ya hay competición. En la LCS hemos tenido por un lado malas noticias: los visados pueden interrumpir la carrera de varios jugadores. Por otro lado, Markz ha anunciado varias mejoras para la liga (que envidiamos desde LEC). Finalmente hemos hecho nuestra tierlist de ADCs de LEC. APÓYANOS AQUÍ https://www.patreon.com/Esportmaniacos https://www.twitch.tv/esportmaniacos 🔁Nuestras redes🔁 https://twitter.com/Esportmaniacos https://www.tiktok.com/@esportmaniacos 💙Referido de AMAZON: https://amzn.to/36cVx3g 00:00:00 - Intro (hoy hablamos de vacas con el flequillo de Marhoder) 00:19:00 - Primer día de LPL 00:24:12 - Primer día de LCK 00:28:40 - Primeras impresiones de la nueva season 00:43:40 - Problemas de visado en LCS a VARIOS JUGADORES 00:52:30 - En LCS Riot les paga bootcamp a Corea para mejorar, mejor formato que LEC... 01:22:00 - Riot quita prizepools en LCK, LCS, LEC 01:34:00 - Nuevo teaser de la LEC 01:45:30 - ¡Tierlist de ADCs de LEC!
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/EBAC information, and to apply for credit, please visit us at PeerView.com/THG865. CME/EBAC credit will be available until January 10, 2027.Precision Tactics With HER2-Targeting ADCs in HER2-Altered Solid Tumors: Candid Conversations and Clinical Consults In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PTK865. CME/MOC/NCPD/AAPA/IPCE credit will be available until January 16, 2027.Forging New Paths With Earlier Use of ADCs in Breast Cancer: From Clinical Breakthroughs to Improved Outcomes In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and GRASP. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Daiichi Sankyo, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/EBAC information, and to apply for credit, please visit us at PeerView.com/THG865. CME/EBAC credit will be available until January 10, 2027.Precision Tactics With HER2-Targeting ADCs in HER2-Altered Solid Tumors: Candid Conversations and Clinical Consults In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PTK865. CME/MOC/NCPD/AAPA/IPCE credit will be available until January 16, 2027.Forging New Paths With Earlier Use of ADCs in Breast Cancer: From Clinical Breakthroughs to Improved Outcomes In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and GRASP. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Daiichi Sankyo, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/PTK865. CME/MOC/NCPD/AAPA/IPCE credit will be available until January 16, 2027.Forging New Paths With Earlier Use of ADCs in Breast Cancer: From Clinical Breakthroughs to Improved Outcomes In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and GRASP. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AstraZeneca and Daiichi Sankyo, Inc.Disclosure information is available at the beginning of the video presentation.
This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/EBAC information, and to apply for credit, please visit us at PeerView.com/THG865. CME/EBAC credit will be available until January 10, 2027.Precision Tactics With HER2-Targeting ADCs in HER2-Altered Solid Tumors: Candid Conversations and Clinical Consults In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Daiichi Sankyo, Inc.Disclosure information is available at the beginning of the video presentation.
Good morning from Pharma Daily: the podcast that brings you the most important developments in the pharmaceutical and biotech world. Today, we delve into a series of transformative updates reshaping drug development and patient care across the globe.Starting with a major collaboration between Roche and Medilink Therapeutics that has captured industry attention. Roche is making a strategic move by committing $570 million to partner on an antibody-drug conjugate, or ADC, targeting the B7-H3 immune checkpoint protein. This partnership underscores a broader industry trend focusing on immuno-oncology. ADCs have become pivotal due to their ability to deliver cytotoxic agents precisely to tumor cells, reducing systemic exposure and minimizing side effects. This precision not only enhances efficacy but also improves patient experience, marking a significant stride in cancer treatment modalities.In another strategic alliance, Pfizer has entered into a $50 million deal with Madrigal Pharmaceuticals for a DGAT2 inhibitor. Madrigal plans to pair this with its liver disease treatment, Rezdiffra, aiming to amplify therapeutic outcomes in liver conditions. This highlights an increasingly popular approach in medicine: polypharmacy and combination therapies. By tackling diseases from multiple angles, these therapies promise more comprehensive management of complex conditions, reflecting a shift towards more personalized and effective treatment strategies.Turning our attention to the startup landscape, "Baby KJ" Scientist has launched a new personalized CRISPR therapy company with $16 million in initial funding from Menlo Ventures. This venture signals growing interest in CRISPR technology for crafting bespoke genetic therapies. The potential for CRISPR lies in its ability to edit genomes precisely, opening possibilities for treating genetic disorders at their root cause and tailoring interventions to individual patients' genetic profiles.On the financial front, Aktis Oncology's successful IPO stands out, raising an impressive $318 million through an upsized offering. This achievement not only illustrates investor confidence in biotech but also suggests a more favorable atmosphere for upcoming biotech ventures seeking public funding. A robust financial ecosystem is crucial for fostering innovation and bringing cutting-edge therapies from the lab bench to the bedside.In another exciting development, Airnexis Therapeutics has secured $200 million to advance its COPD treatment asset in collaboration with a Chinese pharmaceutical firm. The total deal could reach up to $955 million in what's known as biobucks—a term used for milestone payments in biotech partnerships. This collaboration exemplifies the globalization of biotech partnerships, emphasizing the strategic importance of tapping into diverse markets for drug development and commercialization.Meanwhile, Ollin Biosciences is making waves with promising results from its bispecific antibody trial. The antibody showed superior efficacy in treating diabetic macular edema compared to Genentech's Vabysmo. This success potentially sets a new benchmark for retinal disease therapies and highlights the rapid evolution of bispecific antibodies. These agents can engage multiple targets simultaneously, offering enhanced therapeutic potential across various conditions.Leadership dynamics are also influencing the sector. Charles Fuchs has transitioned from his role as Roche's Global Head of Oncology and Hematology Product Development to Tubulis. Such moves suggest potential shifts in strategic focus for both companies involved, reflecting broader trends in leadership realignments within the industry. Additionally, Illumina's appointment of Eric Green as Chief Medical Officer showcases another instance of experienced leaders taking pivotal roles within companies at the forefront of genomic research. Such appointments underscore the imSupport the show
Featuring perspectives from Dr Javier Cortés, Dr Rita Nanda, Prof Peter Schmid and Dr Priyanka Sharma, including the following topics: Introduction (0:00) Case: A woman in her early 80s with multiple comorbidities and triple-negative breast cancer (TNBC) develops bone-only metastases 4 months after declining capecitabine for post-neoadjuvant residual disease — Justin Favaro, MD, PhD (1:50) Case: A woman in her mid 70s with ER-negative, HER2-low (IHC 1+), PIK3CA-mutated, PD-L1-positive metastatic breast cancer (mBC) after receiving 3 cycles of neoadjuvant paclitaxel/carboplatin/pembrolizumab, which was discontinued — Alan Astrow, MD (6:47) Previously Untreated Metastatic TNBC (mTNBC) — Prof Schmid (10:47) Case: A woman in her early 80s with multiregimen-recurrent ER-positive, HER2-low (IHC 1+) ESR1-mutant mBC receives sacituzumab govitecan — Jennifer Yannucci, MD (27:19) Case: The role of datopotamab deruxtecan (Dato-DXd) for patients with ER-positive, HER2-low mBC who experienced disease progression on prior trastuzumab deruxtecan (T-DXd) — Ranju Gupta, MD; Case: A woman in her late 70s with bilateral recurrence in the lungs of ER-negative, HER2-low (IHC 1+) breast cancer (PD-L1 TPS 20%) receives Dato-DXd with durvalumab on protocol — Yanjun Ma, MD, PhD (31:35) Integrating Antibody-Drug Conjugates (ADCs) into the Management of Endocrine-Resistant Hormone Receptor-Positive mBC — Dr Sharma (36:31) Case: A woman in her early 70s with recurrent ER-negative, HER2-low (IHC 2+) mBC receives sacituzumab govitecan and achieves complete remission — Dr Gupta; Case: Management of neutropenia associated with sacituzumab govitecan — Gigi Chen, MD (50:30) Case: A woman in her late 60s with recurrent ER-negative, HER2-low (IHC 1+) mBC (HER2 V69L mutation) receives T-DXd and achieves a complete response but develops Grade 1 interstitial lung disease — Dr Gupta; Case: Management of T-DXd-related side effects — Laila Agrawal, MD (54:10) Selection and Sequencing of Therapy for Relapsed/Refractory mTNBC — Dr Nanda (58:59) Case: A woman in her early 40s with multiregimen-recurrent ER-positive, HER2-low mBC who has experienced severe nausea with past treatments is about to initiate T-DXd — Atif M Hussein, MD, MMM (1:12:40) Tolerability and Other Practical Considerations with ADCs and Other Cytotoxic Agents for mBC — Dr Cortés (1:18:10) CME information and select publications
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, so a larger population than we've seen yet for the T-DXd trials, and saw that not only did they delay progression of brain metastases and result in shrinkage of existing untreated brain mets, but that patients who develop a new brain met, they could stay on the same assigned treatment. They got stereotactic radiation, and then the patients who were on tucatinib with trastuzumab and capecitabine had a further delay in progression of brain mets compared to those on the placebo arm, even after treatment of a new one that developed on treatment. So, I think it's hard. I think most of us for a lot of brain mets might start with the tucatinib approach, but T-DXd is also a very important treatment. You know, you're kind of trading off a diarrhea, some liver enzyme elevations with tucatinib versus nausea, which you really have to work on managing because it can be long-delayed nausea, and this risk of ILD, interstitial lung disease, that's about 12%, with most but not all trials showing a mortality rate from interstitial lung disease of just under 1 percent. In the early-stage setting, it was really interesting to see that with T-DXd getting four cycles in the neoadjuvant setting, a lot less ILD noted than the patients who got up to 14 cycles, as I think they got a median of 10 cycles in the post-surgical setting, there was a little bit more ILD. But I think we're going to be better and better at finding this earlier and preventing mortality by just stopping drug and treating earlier with steroids. Dr. Monty Pal: And this ILD issue, it always seems to resurface. There are drugs that I use in my kidney cancer clinic, everolimus, common to perhaps the breast cancer clinic as well, pembrolizumab, where I think the pattern of pneumonitis is quite different, right? What is your strategy for recognizing pneumonitis early in this context? Dr. Hope Rugo: Well, it is, and you know, having done the very early studies in everolimus where we gave it in the neoadjuvant setting and we're like, "Hmm, the patient came in with a cough. What's going on?" You know, we didn't know. And you have mouth sores, you know, we were learning about the drug as we were giving it. What we don't do with everolimus and CDK4/6 inhibitors, for example, is grade 1 changes like radiation pneumonitis, we don't stop, we don't treat it. We only treat for symptoms. But because of the mortality associated with T-DXd, albeit small, we stop drug for grade 1 imaging-only asymptomatic pneumonitis, and some of us treat with a half dose of steroids just to try and hasten recovery. We've actually now published or presented a couple of datasets from trials, a pooled analysis and a real-world analysis, that have looked at patients who were retreated after grade 1 pneumonitis or ILD and tolerated drug very well and none of them died of interstitial lung disease, which was really great to see because you can retreat safely and some of these patients stayed on for almost a year benefiting from treatment. So, there's a differential toxicity profile with these drugs and there are risk factors which clearly have identified those at higher risk: prior ILD, for example. A French group said smoking; other people haven't found that, maybe because they smoked more in France, I don't know. And being of Japanese descent is quite interesting. The studies just captured that you were treated in Japan, but I think it's probably being of Japanese descent with many drugs that increases your risk of ILD. And, you know, older patients, people who have hypoxia, those are the patients. So, how do we do this? With everolimus, we don't have specific monitoring. But for T-DXd we do; we do every nine weeks to start with and then every 12 weeks CT scans because most of the events occur relatively early. Somebody who's older and at higher risk now get the first CT at six weeks. Dr. Monty Pal: This is super helpful. And I have to tell you, a lot of these drugs are permeating the bladder cancer space which, you know, is ultimately going to be a component of my practice, so thank you for all this. We could probably stay on this topic of HER2-positive disease forever. I'm super interested in that space still. But let me shift gears a little bit and talk about triple-negative breast cancer and this evolving space of HR-positive, HER2-low breast cancer. I mean, tell us about ADCs in that very sort of other broad area. Dr. Hope Rugo: So triple-negative disease is the absolute hardest subset of disease that we have to treat because if you don't have a great response in the early stage setting, the median survival is very short, you know, under two years for the majority of TNBCs, with the exception of the small percentage of low proliferative disease subsets. The co-question is what do we do for these patients and how do we improve outcome? And sacituzumab govitecan has been one strategy in the later line setting that was shown to improve progression-free and overall survival, the Trop-2 ADC. We had recently three trials presented with the two ADCs, sacituzumab govitecan and the other Trop-2 ADC that's approved for HR-positive disease, datopotamab deruxtecan. And they were studied in the first-line setting. Two trials with SG, sacituzumab govitecan, those trials, one was PD-L1 positive, ASCENT-04. That showed that SG with a checkpoint inhibitor was superior, so pembrolizumab was superior to the standard KEYNOTE-355 type of treatment with either a taxane or gemcitabine and carboplatin with pembrolizumab for patients who have a combined positive score for PD-L1, 10 or greater. So, these are patients who are eligible for a checkpoint inhibitor, and SG resulted in an improved progression-free survival. The interesting thing about that dataset is that few patients had received adjuvant or neoadjuvant checkpoint inhibitor, which is fascinating because we give it to everybody now. But access is an issue and timing of the study enrollment was an issue. The other thing which I think we've all really applauded Gilead for is that there was automatic crossover. So, you could get from the company, to try and overcome some of the enormous disparities worldwide in access to these life-saving drugs, you could get SG through the company for free once you had blinded independent central review confirmation of disease progression. Now, a lot of the people who got the SG got it through their insurance, they didn't bill the company, but 80 percent of patients in the control arm received SG in the second-line setting. So that impacts your ability to look at overall survival, but it's an incredibly important component of these trials. So then at ESMO, we saw the data from SG and Dato-DXd in the first-line metastatic setting for patients who either had PD-L1-negative disease or weren't eligible for an immunotherapy. For the Dato study, TROPION-Breast02, that was 10 percent of the patients who had PD-L1-positive disease but didn't get a checkpoint inhibitor, and for the ASCENT-03 trial population it was only 1 percent. Importantly, the trials allowed patients who relapsed within a year of receiving their treatment with curative intent, and the Dato study, TB-02, allowed patients who relapsed while on treatment or within the first six months, and that was 15 percent of the 20 percent of early relapsers. The ASCENT trial, ASCENT-03, had 20 percent who relapsed between 6 and 12 months. The drugs were better than standard of care chemotherapy, the ADCs in both trials, which is very nice. Different toxicity profiles, different dosing intervals, but better than standard of care chemotherapy in the disease that's hardest for us to treat. And importantly, when you looked at the subset of early relapsers, those patients also did better with the ADC versus chemotherapy, which is incredibly important. And we were really interested in that 15 percent of patients who had early relapse. I actually think that six months thing was totally contrived, invented, you know, categorization and doesn't make any sense, and we should drop it. But the early relapsers were 15 percent of TB-02 and Dato was superior to standard of care chemo. We like survival, but the ASCENT trial again allowed the crossover to an approved ADC that improved survival and 80 percent of patients crossed over. In the Dato trial, they did not allow crossover, they didn't provide Dato, which isn't approved for TNBC but is for HR-positive disease, and they didn't allow, of course, pay for SG. So very few patients actually crossed over in their post-treatment data and in that study, they were able to show a survival benefit. So actually, I think in the U.S. where we can use approved drugs already before there's a fixed FDA approval, that people are already switching to use SG or Dato in the first-line setting for metastatic TNBC that's both PD-L1 positive for SG and PD-L1 negative for both drugs. And I think understanding the toxicity profiles of the two drugs is really important as well as the dosing interval to try and figure out which drug to use. Dr. Monty Pal: Brilliant. Brilliant. Well, I'm going to shift gears a little bit. ADCs are a topic, again, just like HER2-positive disease we could stay on forever. Dr. Hope Rugo: Huge. Yes. Dr. Monty Pal: But we're going to shift gears to another massive topic, which is oral SERDs. In broad strokes, right, this utilization of CDK4/6 inhibitors in the context of HR-positive breast cancer is obviously, you know, a paradigm that's been well established at this point. Where do we sequence in oral SERDs? Where do they fit into this paradigm? Dr. Hope Rugo: Ha! This is a rapidly changing area; we keep changing what we're saying every other minute. And I think that there are three areas of great interest. So one is patients who develop ESR1 mutations that allow constitutive signaling through the estrogen receptor, even when there's not estrogen around, and that is a really important mutation that is subclonal; it develops under the pressure of treatment in about 40 percent of patients. And it doesn't happen when you first walk in the door. And what we've seen is that oral SERDs as single agents are better than standard single-agent endocrine therapy in that setting. The problem that we've had with that approach is that we're now really interested in giving targeted agents with our endocrine therapies, not just in the first-line setting where CDK4/6 inhibitors are our standard of care with survival benefit for ribociclib and, you know, survival benefit in subsets with other CDK4/6 inhibitors, and abemaciclib with a numeric improvement. So we give it first line. The question is, what do you do in the second-line setting? Because of the recent data, we now believe that oral SERDs should be really given with a targeted agent. And some datasets which were recently presented, which I think have helped us with that, have been EMBER-3 and then the most recently evERA BC, or evERA Breast Cancer, that looked at the oral SERD giredestrant with everolimus compared to standard of care endocrine therapy with everolimus, where 100 percent of patients received prior CDK4/6 inhibitor and showed a marked improvement in progression-free survival, including in the subsets of patients with a short response, 6-12 months of prior response to CDK4/6 inhibitor and in those who had a PIK3CA pathway mutation. The thing is that the benefit looks like it's much bigger in the ESR1 mutant population, although response was better, PFS wasn't better in the wild type. So, we're still trying to figure that out. We also saw EMBER-3 with imlunestrant and abemaciclib as a second line. Not everybody had had a prior CDK4/6 inhibitor; they compared it to imlunestrant alone, but still the data was quite striking and seemed to cross the need for ESR1 mutations. And then lastly, we saw data from the single arms of the ELEVATE trial looking at elacestrant with everolimus and abemaciclib and showed these really marked progression-free survival data, even though single-arm, that crossed the mutation status. At least for the everolimus combination, abemaciclib analysis is still to come in the mutated subgroups. But really remarkable PFS, much longer. Single-agent fulvestrant after CDK4/6 inhibitor AI has a PFS in like the three-month range and in some studies, maybe close to five months. These are all at 10-plus months and really looking very good. And so those questions are, is it ESR1 mutation alone? Is it all comers? We'd like all comers, right? We believe in the combination approach and we're learning more about combinations with drugs like capivasertib and other drugs as we move forward. Everybody now wants to combine their targeted agent with an oral SERD because they're clearly here to stay with quite remarkable data. The other issue, so the second issue in the metastatic setting is, does it make a difference if we change to an oral SERD before radiographic imaging evidence of progression? And that was the question asked in the SERENA-6 trial where patients had serial monitoring for the presence of ESR1 mutations in ctDNA. And those who had them without progression on imaging could be randomized to switch to camizestrant with the same CDK4/6 inhibitor or stay on their same AI CDK4/6 inhibitor. And they showed a difference in progression-free survival that markedly favored camizestrant. But interestingly, the people who were on the standard control arm had an ESR1 mutation, we think AIs don't work, they stayed on for nine more months. The patients who were on the camizestrant stayed on for more than 16 months. And they presented some additional subset data which showed the same thing: follow-up PFS data, PFS2, all beneficial in SERENA-6 at the San Antonio [Breast Cancer Symposium]. So, we're still a little bit unclear about that. They did quality of life, and pain was markedly improved. They had a marked delayed time to progression of pain in the camizestrant arm. So this is all a work in progress, trying to understand who should we switch without progression to an oral SERD based on this development of this mutation that correlates with resistance. And, you know, it's interesting because the median time to having a mutation was 18 months and the median time to switch was almost 24 months. And then there were like more than 3,000 patients who hadn't gotten a mutation, hadn't switched, and were still okay. So screening everybody is the big question, and when you would start and who you would change on and how this affects outcome. Patients didn't have access to camizestrant in the control arm, something we can't fix but we have experimental drugs. We're actually planning a trial, I hope in collaboration with the French group Unicancer, and looking at this exact question. You know, if you switch and you change the CDK4/6 inhibitor and then you also allow crossover, what will we see? Dr. Monty Pal: We're coming right to the tail end of our time here, and I could probably go on for another couple of hours with you here. But if you could just give us maybe one or two big highlights from San Antonio, any thoughts to leave our audience with here based on this recent meeting? Dr. Hope Rugo: Yeah, I mean, I talked about a lot of those new data already from San Antonio, and the one that I'd really like to mention which I think was, you know, there were a lot of great presentations including personalized screening presented from the WISDOM trial by my colleague Laura Esserman, fascinating and really a big advance. But lidERA was the big highlight, I think, outside of the HER2CLIMB-05 which I talked about earlier in HER2-positive disease. And this study looked at giredestrant, the oral SERD versus standard of care endocrine therapy as treatment for medium and high-risk early-stage breast cancer. And what they showed, which I think was really remarkable with just about a three-year median follow-up, was an improvement in invasive disease-free survival with a hazard ratio of 0.7. I mean, really quite remarkable and so early. It looked as though this was all driven by the high-risk group, which makes sense, not the medium risk, it's too early. And also that there was a bigger benefit in patients who were on tamoxifen compared to giredestrant versus AI, but for both groups, the confidence intervals didn't cross 1. There's even a trend towards overall survival, even though it's way too early. I think that, you know, really well-tolerated oral drug that could improve outcome in early-stage disease, this is the first advance we've seen in over two decades in the treatment of early-stage hormone receptor-positive disease with just endocrine therapy. I think we think that we don't want to give up CDK4/6 inhibitors because we saw a survival benefit with abemaciclib and a trend with giving ribociclib in the NATALEE trial. So we're thinking that maybe one approach would be to give CDK4/6 inhibitors and then switch to an oral SERD or to have enough data to be able to give oral SERDs with these CDK4/6 inhibitors for early-stage disease. And that's all in the works, you know, lots of studies going on. We're going to see a lot of data with both switching 8,000 patients with an imlunestrant switching trial, an elacestrant trial going on, and safety data with giredestrant with abemaciclib and soon to come ribociclib. So, this is going to change everything for the treatment of early-stage breast cancer, and I hope cure more patients of the most common subset of the most common cancer diagnosed in women worldwide. Dr. Monty Pal: Super exciting. It's just remarkable to hear how this has evolved since 25 years ago, which is really the last time I sort of dabbled in breast cancer. Thank you so much, Hope, for joining us today. These were fantastic insights. Appreciate you being on the ASCO Daily News Podcast and really want to thank you personally for your remarkable contribution to the field of breast cancer. Dr. Hope Rugo: Thank you very much, and thanks for talking with me today. Dr. Monty Pal: You got it. And thanks a lot to our listeners today as well. You'll find links to all the studies we discussed today in the transcript of this episode. Finally, if you value the insights that you hear today on the ASCO Daily News Podcast, please rate, review, and subscribe wherever you get your podcasts. Disclaimer: 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 opinion of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Monty Pal @montypal Dr. Hope Rugo @hoperugo Follow ASCO on social media: ASCO on X ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Monty Pal: Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis Dr. Hope Rugo: Honoraria: Mylan/Viatris, Chugai Pharma Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx
Is death the end? Millions have felt the departed reach out, but skepticism remains.Grief psychologist and homicide survivor Dr. Jan Canty offers a deeply investigated, compassionate, and affirming exploration of spontaneous after-death communications (ADCs) by blending decades of clinical experience, personal insights, and riveting stories that counter the stigma of this almost-universal phenomenon.As a clinical psychologist, Jan Canty did not believe in ADCs, even after she experienced one when her husband was brutally murdered. But she could not ignore countless stories from her patients and podcast interviewees as they poured in. A presence, vivid dreams, timely signs—these moments comfort, heal, and assure us that death does not terminate; it transforms.For those mourning, providing grief support, or wondering what awaits them on the other side, Rekindled builds a vital bridge between personal experience and science by:Illuminating the historical, scientific, and cultural shifts that shape our understanding of ADCsExploring how ADCs promote healing and restore connectionIntegrating insights from neuroscience and physicsHighlighting a gap in grief intervention tactics and offering practical tools to caregivers and mental health providersSharing firsthand accounts so no one feels alone in what they've seen, heard, or feltRekindled sheds light on the one experience that connects us all. This is a must-read for fans of Dr. Eben Alexander's Proof of Heaven, and an accessible and needed resource for the grieving, as well as counselors and psychologists, hospice workers, death doulas, and clergy.BioA native Detroiter, Jan Canty, PhD, is a psychologist, writer, photographer, educator, consultant, and cancer survivor. She holds a terminal degree in psychology as well as a post-doctoral fellowship from the Wayne State University School of Medicine, Department of Family Medicine. Dr. Canty has taught psychology at all levels—from community college students to postdoctoral interns. She worked as a forensic psychologist in a large mental hospital for several years. Dr. Canty was awarded Faculty of the Year in her second year of teaching graduate school. She received awards for her photography. Life circumstances delivered her to be uniquely qualified to address surviving murder both from a professional and a personal viewpoint. This is the underpinning of her true- crime memoir, A Life Divided (in print and audiobook formats).Her second book, What Now? Navigating the Aftermath of Homicide and Suicide is a reference book. It is the book she wished she had as a new widow. Dr. Canty also launched a podcast for other homicide survivors entitled Domino Effect of Murder in 2020, now heard in fourteen countries, wherein some guests cautiously told their stories for the first time. Others were already center stage, such as Cook County sheriff's lead investigator, Detective Jason Moran, who works to find answers for families awaiting word on the murders committed by serial murderer John Wayne Gacey.In August of About the Author 253 2019, she was the only nonlaw enforcement guest to speak at the International Association for Identification, the oldest and largest forensic association in the world. In addition, she has been a contributor to Death Investigator Magazine, a digital publication for the death- investigator community. Dr. Canty also administers a private Facebook group (Homicide Survivors and Thrivers) for survivors struggling with grief after homicide. These endeavors opened a rich network of consultants who've generously con tributed to this book. Dr. Canty has appeared as a guest on many podcasts both in the United States and internationally. She presently lives and works (as a consultant) for the federal government and spends her free time with her family, friends, and two Saint Bernards, and continuing her photography, gardening, writing, and traveling.https://jancantyphd.com/https://www.amazon.com/dp/B0D2Q1WV3W https://www.pastliveshypnosis.co.uk/https://www.patreon.com/ourparanormalafterlifeMy book 'Verified Near Death Experiences' https://www.amazon.com/dp/B0DXKRGDFP Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.
Is death the end? Millions have felt the departed reach out, but skepticism remains.Grief psychologist and homicide survivor Dr. Jan Canty offers a deeply investigated, compassionate, and affirming exploration of spontaneous after-death communications (ADCs) by blending decades of clinical experience, personal insights, and riveting stories that counter the stigma of this almost-universal phenomenon.As a clinical psychologist, Jan Canty did not believe in ADCs, even after she experienced one when her husband was brutally murdered. But she could not ignore countless stories from her patients and podcast interviewees as they poured in. A presence, vivid dreams, timely signs—these moments comfort, heal, and assure us that death does not terminate; it transforms.For those mourning, providing grief support, or wondering what awaits them on the other side, Rekindled builds a vital bridge between personal experience and science by:Illuminating the historical, scientific, and cultural shifts that shape our understanding of ADCsExploring how ADCs promote healing and restore connectionIntegrating insights from neuroscience and physicsHighlighting a gap in grief intervention tactics and offering practical tools to caregivers and mental health providersSharing firsthand accounts so no one feels alone in what they've seen, heard, or feltRekindled sheds light on the one experience that connects us all. This is a must-read for fans of Dr. Eben Alexander's Proof of Heaven, and an accessible and needed resource for the grieving, as well as counselors and psychologists, hospice workers, death doulas, and clergy.BioA native Detroiter, Jan Canty, PhD, is a psychologist, writer, photographer, educator, consultant, and cancer survivor. She holds a terminal degree in psychology as well as a post-doctoral fellowship from the Wayne State University School of Medicine, Department of Family Medicine. Dr. Canty has taught psychology at all levels—from community college students to postdoctoral interns. She worked as a forensic psychologist in a large mental hospital for several years. Dr. Canty was awarded Faculty of the Year in her second year of teaching graduate school. She received awards for her photography. Life circumstances delivered her to be uniquely qualified to address surviving murder both from a professional and a personal viewpoint. This is the underpinning of her true- crime memoir, A Life Divided (in print and audiobook formats).Her second book, What Now? Navigating the Aftermath of Homicide and Suicide is a reference book. It is the book she wished she had as a new widow. Dr. Canty also launched a podcast for other homicide survivors entitled Domino Effect of Murder in 2020, now heard in fourteen countries, wherein some guests cautiously told their stories for the first time. Others were already center stage, such as Cook County sheriff's lead investigator, Detective Jason Moran, who works to find answers for families awaiting word on the murders committed by serial murderer John Wayne Gacey.In August of About the Author 253 2019, she was the only nonlaw enforcement guest to speak at the International Association for Identification, the oldest and largest forensic association in the world. In addition, she has been a contributor to Death Investigator Magazine, a digital publication for the death- investigator community. Dr. Canty also administers a private Facebook group (Homicide Survivors and Thrivers) for survivors struggling with grief after homicide. These endeavors opened a rich network of consultants who've generously con tributed to this book. Dr. Canty has appeared as a guest on many podcasts both in the United States and internationally. She presently lives and works (as a consultant) for the federal government and spends her free time with her family, friends, and two Saint Bernards, and continuing her photography, gardening, writing, and traveling.https://jancantyphd.com/https://www.amazon.com/dp/B0D2Q1WV3W https://www.pastliveshypnosis.co.uk/https://www.patreon.com/ourparanormalafterlifeMy book 'Verified Near Death Experiences' https://www.amazon.com/dp/B0DXKRGDFP Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.
In this podcast, Brian and Tom engage with Pedro Barata to discuss the emerging field of bispecific T cell engagers and antibody-drug conjugates (ADCs) in the treatment of prostate cancer. They explore the promising data surrounding these therapies, the challenges faced in clinical trials, and the implications of phase three studies. The discussion also touches on the comparative development of ADCs in prostate cancer versus bladder cancer, highlighting the unique challenges and opportunities in each area. The conversation concludes with reflections on the future of these therapies and the potential for combination strategies to enhance treatment efficacy
Welcome to the Oncology Brothers podcast! In this episode, we dived into the key highlights from the SABCS 2025 conference, focusing on metastatic hormone receptor-positive breast cancer. Join us as we discussed: • The role of CDK4-6 inhibitors in frontline therapy, featuring updates from the AMBRE and MONALEESA-3 studies • Insights into second-line treatment options, including the VIKTORIA-1, evERA, EMBER-3, SERENA-6 trials • A critical look at the ASCENT-07 study, exploring the role of antibody-drug conjugates (ADCs) in endocrine-resistant disease We were thrilled to have Dr. Hope Rugo, a world-renowned breast medical oncologist from City of Hope, share her expertise and insights on these pivotal studies. Tune in for an informative discussion that unpacks the latest advancements in treatment options for metastatic hormone receptor-positive breast cancer, and learn how these findings may impact clinical practice. Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ Don't forget to like, subscribe, and check out our other episodes for more insights on treatment algorithms, recent approvals, and conference highlights! #SABCS2025 #MBC #HRpositive #CDK46 #ADCs #OncologyBrothers
Featuring perspectives from Dr Lisa A Carey and Dr Rita Nanda, including the following topics: Overview: Molecular basis of antibody-drug conjugate (ADC) toxicities — Sequencing of ADCs and mechanisms of resistance (0:00) Case: A woman in her late 60s with localized triple-negative breast cancer develops myocarditis during neoadjuvant therapy with chemotherapy/pembrolizumab — Richard Zelkowitz, MD (8:22) Case: A woman in her mid 70s with recurrent ER-negative, HER2-low, PD-L1-positive metastatic breast cancer (mBC) who experiences disease progression on nab paclitaxel/atezolizumab responds to sacituzumab govitecan — Ranju Gupta, MD (26:43) Case: A woman in her early 80s with recurrent ER-positive, HER2-low (IHC 1+) mBC experiences disease progression on trastuzumab deruxtecan (T-DXd), then receives datopotamab deruxtecan and develops pulmonary symptoms — Laila Agrawal, MD (32:11) Data Review: T-DXd (37:51) Case: A woman in her early 70s with recurrent ER-positive, HER2-low (IHC 1+) mBC, including bladder metastases, experiences disease progression after palbociclib/letrozole, then capivasertib/fulvestrant, then nab paclitaxel — Justin Favaro, MD, PhD (44:02) Case: A woman in her late 70s with ER-positive, HER2-low mBC who experiences disease progression after 1 year of ribociclib/letrozole receives sacituzumab govitecan — Erik Rupard, MD (55:19) CME information and select publications
In this episode of the Oncology Brothers podcast, we are joined by Dr. Komal Jhaveri, a breast medical oncologist at Memorial Sloan Kettering, to discuss the evolving landscape of metastatic hormone receptor positive breast cancer, particularly focusing on low and ultra-low HER2 expression. Key topics include: • The significance of the DESTINY Breast-04 and DESTINY Breast-06 studies and their impact on treatment options. • The definition and implications of low and ultra-low HER2 expression in clinical practice. • The importance of HER2 testing and the dynamic nature of HER2 expression in tumors. • Treatment sequencing strategies, including the use of antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (TDXd) and sasituzumab govitecan. • Management of treatment-related toxicities, including ILD, nausea, and alopecia. Join us for an insightful discussion that aims to keep healthcare professionals updated on the latest advancements in cancer care. Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ Don't forget to subscribe for more episodes and insights!
In this episode of the Oncology Brothers podcast, we dived deep into the world of antibody drug conjugates (ADCs) in non-small cell lung cancer (NSCLC). We welcomed Dr. Jacob Sands from the Dana-Farber Cancer Institute to discuss the latest ADCs approved for NSCLC, including Trastuzumab deruxtecan (TDXd), Datopotamab deruxtecan (Dato-DXd), and Telisotuzumab Vedotin (Teliso-V). We explored the side effect profiles of these therapies, focusing on critical toxicities such as interstitial lung disease (ILD), mucositis, and peripheral neuropathy. Dr. Sands shared valuable clinical pearls on managing these adverse events, emphasized the importance of proactive monitoring and patient education. Key topics covered in this episode: • Overview of ADCs and their role in NSCLC treatment • TDXd: alopecia, ILD, fatigue, nausea/vomiting • Dato-DXd: cytopenias, mucositis, dry eyes • Teliso-V: peripheral neuropathy, fatigue, peripheral edema • The evolving landscape of ADCs and future directions in lung cancer treatment Whether you're a healthcare professional or someone interested in oncology, this episode provides essential insights into the management of side effects associated with these innovative therapies. Tune in for practical advice and expert opinions that can enhance patient care in the community setting. Follow us on social media: • X/Twitter: https://twitter.com/oncbrothers • Instagram: https://www.instagram.com/oncbrothers • Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more episodes on practice-changing discussions in oncology! #ADC #NSCLC #TDXd #DatoDXD #TelisoV #ToxicityManagement #OncologyBrothers
"I'll go back to the backpack analogy. When your kids come home with a backpack, all of a sudden their homework is not on the desk where it's supposed to be. It's in the kitchen; it kind of spreads all over the place, but it's still in the house. When we give antibody–drug conjugates (ADCs), the chemotherapy does go in, but then it can kind of permeate out of the cell membrane and something right next to it—another cancer cell that might not look exactly like the cancer cell that the chemotherapy was delivered into—is affected and the chemotherapy goes over to that cancer cell and kills it," ONS member Marisha Pasteris, OCN®, office practice nurse in the breast medicine service at Memorial Sloan Kettering Cancer Center in New York, NY, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about ADCs in metastatic breast cancer. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 This podcast is sponsored by Gilead and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications. Episode Notes This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 391: Pharmacology 101: Antibody–Drug Conjugates Episode 378: Considerations for Adolescent and Young Adult Patients With Metastatic Breast Cancer Episode 368: Best Practices for Challenging Patient Conversations in Metastatic Breast Cancer Episode 350: Breast Cancer Treatment Considerations for Nurses Episode 303: Cancer Symptom Management Basics: Ocular Toxicities ONS Voice articles: An Oncology Nurse's Guide to Cancer-Related Ocular Toxicities Black Patients With Metastatic Breast Cancer Are Less Informed About Their Clinical Trial Options Communication Case Study: Talking to Patients About Progressive Metastatic Breast Cancer What Is HER2-Low Breast Cancer? ONS Voice drug reference sheets: Belantamab mafodotin-blmf Datopotamab deruxtecan-dlnk Enfortumab vedotin-ejfv Fam-trastuzumab deruxtecan-nxki ONS books: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) Guide to Breast Care for Oncology Nurses Guide to Cancer Immunotherapy (second edition) ONS courses: ONS Fundamentals of Chemotherapy and Immunotherapy Administration™ ONS/ONCC® Chemotherapy Immunotherapy Certificate™ Clinical Journal of Oncology Nursing article: Antibody–Drug Conjugates and Ocular Toxicity: Nursing, Patient, and Organizational Implications for Care The Association Between Hormone Receptor Status and End-of-Life Care Among Patients With Metastatic Breast Cancer Oncology Nursing Forum article: Impact of Race and Area Deprivation on Triple-Negative Metastatic Breast Cancer Outcomes ONS huddle cards: Altered Body Image Huddle Card Chemotherapy Huddle Card Targeted Therapy Huddle Card Foundations of Antibody–Drug Conjugate Use in Metastatic Breast Cancer: A Case Study ONS Biomarker Database (refine by breast cancer) ONS Breast Cancer Learning Library American Society of Clinical Oncology (ASCO) homepage Drugs@FDA package inserts National Comprehensive Cancer Network homepage Susan G. Komen metastatic breast cancer page To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode "What an ADC is doing is taking the antibody and linking it to a cytotoxic chemotherapy with the idea of delivering it directly into the cell. How I explain this to new nurses or patients is a backpack analogy. If we think of it as a HER2 molecule wearing a chemo backpack, it's going to find the HER2 receptor attached to it and then drop the chemotherapy into the cell via the backpack. Similar to how we come home from work, we open the key to our door, we're carrying all of our items, and then we drop our own personal items in our house." TS 2:30 "The reason that so many patients with metastatic breast cancer are able to receive ADC therapy is because they are targeting two very common antibodies that we see in breast cancer. One is HER2 and the other is trophoblast cell surface antigen 2 (TROP2). These are seen across the board. We see these on triple-negative breast cancers, hormone receptor–positive cancers, and HER2-positive breast cancers. And now we have a new way to talk about HER2, which is a HER2-low. ... Recently, we have found that patients who express low levels of HER2 are able to receive ADC therapy, specifically fam-trastuzumab deruxtecan." TS 4:21 "Another [ADC] that has just been approved is datopotamab deruxtecan. This is another ADC that targets the TROP2 receptor on a cancer cell. This one carries a lot of side effects. I mentioned earlier that you need an ophthalmology clearance because there is a lot of ocular toxicity around this one. We see a lot of blepharitis, conjunctivitis, there can be blurred vision. Another thing we monitor on this one is mucositis. In the package insert, there's a recommendation for using ice chips while receiving the treatment. ... Then in the HER2-positive and HER2-low space is the big one, which is fam-trastuzumab deruxtecan. This was approved in 2019 for the HER2-positive patients, then more recently in the HER2-low [patients]. The big [side effect] with this one is interstitial lung disease." TS 10:11 "Interstitial lung disease is an inflammation or a little bit of fibrosis within the lung that causes an impaired exchange between the oxygen and carbon dioxide. This was seen in the clinical trials, specifically around fam-trastuzumab deruxtecan. During the trials, they had a very small percentage, I think it was 1%, that died due to interstitial lung disease. So, this is a very important side effect for us as nurses to be aware of. It typically presents in patients like a dyspnea. A lot of times, it's like, 'Well, I used to be able to walk my kid to the bus stop, but now when I walk there, I feel really short of breath.' Or 'I've had this dry cough for the past couple weeks and I've tried medications, but haven't had that relieved.' So, we really need to be aware of that because early intervention in interstitial lung disease is key." TS 12:57 "ADCs are toxic drugs. They have the benefit of being targeted, but we know that they carry a lot of side effects. ... Their specificity makes them so wonderful and we've seen amazing responses to these drugs. But also, we want patients to be safe. We want to give these drugs safely. So, we have to assess our patients and make sure that this is an appropriate patient to give this therapy to. I think that's an open conversation that clinicians need to have with patients regarding these drugs." TS 18:08
"Antibody–drug conjugates (ADCs) have three basic parts: the antibody part, the cytotoxic chemo, and the linker that connects the two. First, the antibody part binds to the target on the surface of the cell. Antibodies can be designed to bind to proteins with a very high level of specificity. That's what gives it the targeted portion. Then the whole thing gets taken up by the cell and broken down, which releases the chemotherapy part. Some sources will call this the 'payload' or the 'warhead.' That's the part that's attached to the 'heat-seeking' part, and that's what causes the cell death," Kenneth Tham, PharmD, BCOP, clinical pharmacist in general oncology at the University of Washington Medicine and Fred Hutchinson Cancer Center in Seattle, WA, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about antibody–drug conjugates. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by November 28, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learners will report an increase in knowledge related to the mechanism of action of antibody–drug conjugates. Episode Notes Complete this evaluation for free NCPD. ONS Podcast™ episodes: Pharmacology 101 series Episode 303: Cancer Symptom Management Basics: Ocular Toxicities Episode 283: Desensitization Strategies to Reintroduce Treatment After an Infusion-Related Reaction ONS Voice articles: An Oncology Nurse's Guide to Cancer-Related Ocular Toxicities Antibody–Drug Conjugates Join the Best of Two Worlds Into One New Treatment Nursing Management of Adverse Events From Enfortumab Vedotin Therapy for Urothelial Cancer Oncology Nurses' Role in Translating Biomarker Testing Results The Pharmacist's Role in Combination Cancer Treatments ONS Voice drug reference sheets: Belantamab mafodotin-blmf Datopotamab deruxtecan-dlnk Enfortumab vedotin Fam-trastuzumab deruxtecan-nxki ONS book: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) ONS course: ONS Fundamentals of Chemotherapy and Immunotherapy Administration™ Clinical Journal of Oncology Nursing articles: Antibody–Drug Conjugates and Ocular Toxicity: Nursing, Patient, and Organizational Implications for Care Nurse-Led Grading of Antineoplastic Infusion-Related Reactions: A Call to Action Other ONS resources: Antineoplastic Administration Huddle Card Biomarker Database Chemotherapy Huddle Card Monoclonal Antibodies Huddle Card Association of Cancer Care Centers (ACCC) antibody–drug conjugates page Drugs@FDA Hematology/Oncology Pharmacy Association (HOPA) National Cancer Institute cancer drugs page Network for Collaborative Oncology Development and Advancement (NCODA) clinical resource library ACCC/HOPA/NCODA/ONS Patient Education Sheets website To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org Highlights From This Episode "The mechanism of action of the chemo itself depends on what agent or what 'warhead' is attached. Generally, [ADCs] have some kind of cytotoxic mechanism related to many of the chemotherapies that we use in practice, without attachment to the antibody. Some of them can be microtubule inhibitors, vinca alkaloids like vincristine. Some of them can be topoisomerase I (TOP1) inhibitors like irinotecan. Some can be alkylating agents that cause DNA breaks. So, again, looking back at the arsenal we have of cytotoxic chemo, these can all be incorporated into the ADCs." TS 5:54 "I want to talk about a case where the biomarker is being tested, but the biomarker isn't the target that you're looking for. One good case of this is a newer agent that was approved called datopotamab deruxtecan. The datopotamab portion is specific to a target called 'trophoblast cell surface antigen 2' (TROP2), which is expressed on the surface of many epithelial cancers. This agent was first approved in hormone receptor-positive, HER2-negative breast cancer, and received accelerated approval in patients with non-small cell lung cancer (NSCLC) with an EGFR mutation. ... The antibody looks for a target, TROP2. But in both of these cases—in the breast cancer and the NSCLC—you're testing for expression of different mutations or lack thereof. You're not looking for expression of TROP2. There's more research that needs to be done about the relationship between TROP2 expression and the presence or absence of these other biomarkers, but until we know more, we're actually testing for biomarkers that aren't the target of the ADC." TS 10:22 "There are common adverse advents to antibodies and chemo in general. Because we have both of these components, we want to watch out for the adverse effects of both of them. Antibodies, as with most proteins, can trigger an immune response or an infusion reaction. So, many ADCs can also cause hypersensitivity or infusion reactions. The rates of that are really variable and depend on the actual antibodies themselves. Then you have the cytotoxic component, the chemotherapy component, which has its own characteristic side effects. So, if we think of general chemo side effects—fatigue, nausea, bone marrow suppression, alopecia—these can [occur] with a lot of ADCs as well." TS 15:34 "The rate of ocular toxicity in [mirvetuximab soravtansine] is quite high. The manufacturer reports that this can occur in up to 60% of patients. With rates so high, the manufacturer recommends a preventive strategy. For this particular agent, [they] recommend patients have required eyecare. ... This ocular toxicity is something we do see in other ADCs that don't have the same target and don't necessarily have the same payload component. For example, tisotumab vedotin and again, datopotamab deruxtecan, can both cause ocular toxicities and both would have required ocular supportive care." TS 20:08 "Overall, I feel like the future is incredibly bright for these agents. There have only been around a dozen therapies approved by the U.S. Food and Drug Administration (FDA) despite this idea—the first agent came out in 2000. So, 25 years later, there are only around a dozen FDA-approved treatments. But there are so many more that are coming through the pipeline. And as we're discovering more biomarkers and developing more specialized antibodies, it's only natural that more ADCs will follow." TS 26:50
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