Podcasts about nsclc

In this episode, recorded in Mandarin, host Dr. Chunxia Su leads a discussion about early stage and preoperative care for patients with NSCLC with an EGFR mutation. Guests: Wenzhao Zhong, Deputy Prensendent of Guangdong Provincial People's Hospital, Director of the Cancer Institute, Guangdong Provincial People's Hospital Jie Hu， Deputy director, Department of Respiratory Medicine, Shanghai Geriatric Medical Center，Zhongshan Hospital, Fudan University Min Fan M D， Deputy Director , Department of Radiation Oncology, Fudan University Shanghai Cancer Center

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 podcast, experts Jacob Sands, MD; Marina Chiara Garassino, MD; and Eric Singhi, MD; use realistic cases to explore key decision points in applying HER2- and TROP2-targeted therapies across the non–small cell lung cancer (NSCLC) continuum, including patient selection, sequencing, and toxicity management.

In this podcast, experts Christine M. Lovly, MD, PhD, FASCO; Lyudmila Bazhenova, MD; Hossein Borghaei, DO, MS; and Xiuning Le, MD, PhD, discuss how to sequence systemic therapy based on the molecular profile of non–small cell lung cancer that has progressed on a first-line EGFR-directed tyrosine kinase inhibitor, including discussion on the use of bispecific antibodies in this setting.

As part of IASLC's ongoing series of podcasts in world languages, Dr. Alfredo Addeo moderates a Virtual Tumor Board discussion with Dr. Angela Botticella and Dr. Jean Yannis Perentes. The tumor board focuses on the management of resectable EGFR-mutant NSCLC. Guests: Angela Botticella, MD Radiational Oncologist Department of Radiation Oncology Gustave Roussy Jean Yannis Perentes, MD, PhD Professor and Chief, Department of Thoracic Surgery University Hospital of Lausanne CHUV

This week discuss BR.31 trial of adjuvant durvalumab in NSCLC and put it into the context of the positive studies with atezolizumab and pembrolizumab. We also highlight 2 notable presentations at ASCO GU 2026 on perioperative enfortumab vedotin + pembrolizumab in cisplatin-eligible patients with resectable bladder cancer (KEYNOTE-B15) and advjuant pembrolizumab + belzutifan in RCC (LITESPARK-022) Check out the Oncology Insights Newsletter: https://www.kelleycpharmd.com/newsletter-oncopharm

In this podcast, experts Mara Antonoff, MD, FACS; Laura Alder, MD; and Stephanie Worrell, MD, FACS, discuss the latest advances in immunotherapy and EGFR-targeted treatments for patients with resectable, early-stage, non–small cell lung cancer.

In this episode of Lung Cancer Considered, host Dr. Stephen Liu is joined by Dr. Sara Pilotto and Dr. Jonathan Riess for a virtual tumor board discussion on the management of metastatic EGFR exon 19 NSCLC . Using a complex case featuring discordant biomarker results and brain metastases, the panel explores first-line treatment strategies including osimertinib monotherapy, FLAURA2 (osimertinib plus chemotherapy), and MARIPOSA (amivantamab plus lazertinib), as well as sequencing at progression, re-biopsy, CNS considerations, and the evolving role of local consolidation and clinical trials.

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 a series of remarkable advancements and regulatory evolutions shaping the landscape of medicine.One of the most significant recent developments involves Boehringer Ingelheim's drug Hernexeos, which has seen a rapid expansion in its use as a first-line treatment for non-small cell lung cancer (NSCLC). This expansion was made possible through the FDA's Commissioner's National Priority Voucher, an initiative designed to fast-track the approval of treatments addressing critical needs. This rapid progression highlights a commitment to accelerating access to crucial oncological treatments, emphasizing the role of accelerated regulatory pathways in swiftly delivering innovative therapies to patients who need them the most.In oncology, a combination therapy involving Padcev and Keytruda is showing promising results in improving overall survival rates for patients with muscle-invasive bladder cancer who are eligible for cisplatin. However, the continuously evolving landscape of treatment options for this cancer type means that further evaluation is necessary. This scenario highlights the ever-changing nature of oncology strategies and the ongoing need for clinical validation to determine the most effective treatment regimens.Switching gears to immunology, UCB's Bimzelx has reached a significant sales milestone, reflecting its growing influence in treating multiple indications. This success points to an expanding market for immunology therapeutics, as the industry remains focused on developing blockbuster treatments that can serve various conditions effectively.On the regulatory front, Moderna's combination influenza/COVID-19 vaccine has received a positive review from the European Medicines Agency's Committee for Medicinal Products for Human Use. This green light exemplifies the EU's dedication to thorough scientific evaluations. It contrasts with the FDA, which has exhibited hesitancy in this area, highlighting how varying regulatory approaches can affect drug availability in different regions.The field of HIV treatment is also seeing progress with GSK's ViiV division confirming the efficacy of its long-acting Cabenuva regimen for adolescents over a 96-week period. This long-acting regimen provides an alternative to daily oral therapies, potentially improving adherence and outcomes among younger populations—a crucial factor in managing chronic conditions effectively.Meanwhile, legal developments are stirring as the debate over "skinny labeling" for generic drugs reaches a pivotal point. The U.S. Supreme Court is being urged to overturn a ruling that endangers this pathway, highlighting the fine balance between fostering generic drug competition and protecting pharmaceutical innovation. In related legislative discussions, a Senate hearing focused on the FDA's rare disease review process has brought to light concerns about bureaucratic obstacles that may slow innovation. There is a call from stakeholders for more streamlined processes to ensure timely access to treatments for rare diseases—a sentiment echoed by many in the industry.The burgeoning field of CAR-T cell therapies continues to make waves, especially against solid tumors. Recent preclinical studies have shown potential efficacy in eradicating solid tumors in mice models. Despite these promising findings, significant regulatory challenges remain, and streamlining approval processes could accelerate their clinical application.In other significant news within the industry, Novartis has completed its acquisition of Avidity Biosciences for $12 billion, leading to the creation of Atrium Therapeutics. With a capitalization of $270 million, Atrium emerges with two promising preclinical candidates targeting cardiovascular conditions, signaling potential advSupport the show

In today's episode, we spoke with David Carbone, MD, PhD. Dr Carbone is a professor of internal medicine at The Ohio State University, co-leader of the Translational Therapeutics Program and director of the Thoracic Oncology Center at the Ohio State University Comprehensive Cancer Center–James, as well as the Barbara J. Bonner Chair in Lung Cancer Research in Columbus.In our exclusive interview, Dr Carbone discussed the 6-year data from the phase 3 CheckMate 9LA trial (NCT03215706), which not only reaffirmed the durability of benefit with nivolumab (Opdivo) plus ipilimumab (Yervoy) and chemotherapy but also highlighted particularly strong outcomes in historically poor-prognosis subgroups, including patients with PD-L1–negative tumors and those with squamous histology. Carbone also underscored the safety and tolerability of the regimen. Although dual immunotherapy carries higher toxicity than monotherapy, no new safety signals emerged at 6 years. Carbone also addressed the limitations of current biomarkers. Although PD-L1 remains the primary tool guiding immunotherapy decisions, it is an imperfect predictor. 

In this episode of Lung Cancer Considered, host Dr. Narjust Florez explores the evolving landscape of emerging molecular targets in NSCLC with Dr. Kelsey Pan and Rajat Thawani, live from the Targeted Therapies of Lung Cancer (TTLC) 2026 conference. The discussion highlights rare oncogenic drivers with a focus on clinical evidence, resistance mechanisms and trial design. The episode also addresses biomarker testing, the role of next-generation sequencing and liquid biopsy, and what the next five years may hold for precision treatment strategies in NSCLC. Guests: Kelsey Pan, MD, MPH Assistant Professor of Medicine Department of Hematology & Oncology, Thoracic Medical Oncology Section Emory University Winship Cancer Institute Rajat Thawani, MD Assistant Professor of Medicine Division of Hematology and Oncology Knight Cancer Institute, OHSU

In today's episode, we spoke with Alexander I. Spira, MD, PhD, FACP, FASCO. Dr Spira is co-director of the Virginia Cancer Specialists (VCS) Research Institute in Fairfax, director of the VCS Thoracic and Phase I Program, chief scientific officer of NEXT Oncology, and a clinical assistant professor at Johns Hopkins University in Baltimore, Maryland.In our exclusive interview, Dr Spira discussed the significance of the December 2025 FDA approval of amivantamab and hyaluronidase-lpuj (Rybrevant Faspro), also known as subcutaneous amivantamab, for the treatment of patients with EGFR-mutated non–small cell lung cancer (NSCLC) across all approved indications for amivantamab-vmjw (Rybrevant). He noted key data from the pivotal phase 3 PALOMA-3 trial (NCT05388669), which showed that subcutaneous amivantamab combined with lazertinib (Lazcluze) had a more favorable safety profile compared with intravenous (IV) amivantamab plus lazertinib and was noninferior to the IV formulation in terms of efficacy. Dr Spira contextualized these trial findings within the larger EGFR-mutated NSCLC treatment paradigm and explained how this formulation of amivantamab addresses a previously unmet patient need.

As part of IASLC's ongoing series of Lung Cancer Considered podcasts in world languages, Dr. Molly Li moderates a discussion in Cantonese with two expert cardiothoracic surgeons, Dr. Ben Li, Professor from The First Affiliated Hospital of Guangzhou Medical University and, and Dr. Calvin Ng, Professor from the Chinese University of Hong Kong. The discussion: reviews surgical management of early-stage NSCLC, including VATS, and lobar versus sublobar resection; and explores novel technologies including endobronchial therapy and tubeless anesthesia. Host: Molly Li, MD Clinical Assistant Professor Department of Clinical Oncology, CUHK, Hong Kong Guests: Shuben Li, MD, PhD Professor, Department of Thoracic Surgery National Center for Respiratory Medicine The First Affiliated Hospital of Guangzhou Medical University Calvin S.H. Ng, BSc MBBS, MD Environmental Foundation Professor of Thoracic Surgery Department of Surgery The Chinese University of Hong Kong (CUHK)

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.  

Dr. Joshua Reuss is back on the podcast to discuss the full update to the living guideline on stage IV NSCLC without driver alterations. He discusses the new evidence and how this impacts the latest recommendations on first-line and subsequent therapeutic options. Dr. Reuss emphasizes the need for shared decision-making between clinicians and patients. He shares ongoing research that the panel will review in the future for further updates to this living guideline, and puts the updated recommendations into context for clinicians treating patients with stage IV NSCLC. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer Without 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-25-02825    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. Joshua Reuss from Georgetown University, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2026.3.0." It is great to have you back on the show today, Dr. Reuss. Dr. Joshua Reuss: Happy to be here, Brittany. Brittany Harvey: 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. Reuss who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. Dr. Reuss, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer without driver alterations is updated on an ongoing basis. So, what prompted this latest update to the recommendations? Dr. Joshua Reuss: Our committee is tasked with making routine updates to the living guidelines and really keeping them living, right? So, evaluating new data as it is coming in to see, is this practice changing? Is this data that should inform and potentially alter our guideline recommendations so that practitioners and other care providers could really make the best treatment decisions for their patients? So that is something that happens on a more routine basis, but periodically, we are tasked with performing a more comprehensive update of our guideline where we really evaluate every one of our point recommendations, the data associated with these recommendations, to be sure that these are up to date, these are comprehensive, and to see if we need to alter anything in the language of these updates. Brittany Harvey: Excellent. Thank you for providing that background. And yes, this is truly a comprehensive update that goes through all the latest literature. Given that, I would like to review what has changed and what is new in the recommendations. So, what are the updated recommendations on first-line therapy for patients with stage IV non-small cell lung cancer without driver alterations? Dr. Joshua Reuss: So there are two main guidelines that we recommend from this panel. One is a driver mutation-positive guideline and the other is a driver mutation-negative guideline. And I think on first blush, one might look at kind of the recent flurry of approvals and new data and say, well, all the excitement, you know, is in the driver mutation-positive guideline. But I would say that the driver mutation-negative guideline is equally as important and really has several unique challenges associated with it. You know, first and foremost is that there are really a multitude of regimens that can be considered for any one patient. And how to choose between one can be quite difficult and a stressful challenge that clinicians can have, particularly since there are really no randomized studies comparing these regimens in a head-to-head fashion. In addition, you know, these guidelines are really broken down by two key factors. One is disease histology, so namely squamous versus non-squamous histology. And the other is PD-L1 status, broken down into one of three tertiles: PD-L1 high, which is greater than or equal to 50% expression; PD-L1 low, which is 1% to 49% expression; and then PD-L1 negative or unknown. So what you are really looking at, if you do that math, is really six unique patient subpopulations where we need to make a recommendation on one of the multitude of treatment regimens that is approved. And what that means is you are oftentimes really looking at subset and sub-subset level data to help inform clinicians in their treatment decision making, which can be quite challenging because as those small subsets of data is more and more parsed, there are many confounders that can be interjected there. And so I think the committee is tasked with really quite a challenge in terms of how to really communicate and broadcast that data in a way that informs clinicians in making a decision on what is the right treatment for their patient. Brittany Harvey: Absolutely. It can be challenging to interpret that subgroup data across several different studies that are reporting on different regimens and different outcomes. And I appreciate you mentioning the driver mutation-positive guideline as well. Listeners can check out the companion episode with Dr. Puri for more information on what is changed in the driver mutation-positive guideline. Based on that primer, what is new for first-line therapy for patients with stage IV non-small cell lung cancer without driver alterations? Dr. Joshua Reuss: Even though I will say there is not a lot of new trial data that was incorporated into this guideline, there were some updates and just some meaningful long-term data that we incorporated. I think first and foremost, there is a new top-level recommendation in this guideline pertaining to molecular testing, which is absolutely critical in both the driver mutation-positive and driver mutation-negative space. I think we tend to think that, oh, well, molecular testing really only pertains to then finding a driver mutation. But the lack of a mutation is absolutely critical as well, right? Because that is what leads us down the mutation-negative pathway. We also need this molecular testing to assess PD-L1 status. We are seeing emerging data on molecular mutations that might confer resistance to certain immunotherapy-based strategies. So the committee felt strongly that a recommendation on molecular testing is critical to include in both the driver mutation-positive guideline and the driver mutation-negative guideline. I will also say that we are now seeing five and six-year updates from some of the landmark trials of immunotherapy in driver mutation-negative non-small cell lung cancer. It is really incredible to see that in some of these trials, we are seeing very impressive durability of the treatment in the patient subsets that we are commenting on. In others, perhaps that durability is less clear, and I think that leads to challenges in making a recommendation on any one particular regimen. And I think that is nowhere more clear than in the squamous subset. I think that was one perhaps subtle change that is in this guideline where, particularly in the PD-L1 negative squamous population, the committee felt that no one regimen really was worthy of standing above the others. Sometimes I think it is important to really champion one unique regimen if we feel that the data is there to support it. But I think it is equally important to list multiple regimens where the data is less clear. I think another point is that while perhaps there were no new regimens that we have added or that led to other clear changes in the prioritization of one regimen over another, there are other unique data subsets that I think come into play in making a decision and that really are important when looking at the discussion on any one recommendation from this guideline. For example, we know there is emerging data on perhaps the significance of molecular alterations in KEAP1 or STK11 and how that might influence frontline decision-making. You know, there is not a prospective phase III trial in this population, but I think we still need to use that data in certain scenarios to make recommendations for a particular patient. Another example of a trial that, again, did not change our recommendations, but I think one can incorporate in their decision making is the KEYNOTE-598 trial. Now, this is not a new study, but what it studied was pembrolizumab versus pembrolizumab plus ipilimumab in a PD-L1 high subset, and found that the addition of ipilimumab to pembrolizumab in the PD-L1 high population did not significantly improve clinical efficacy. And so while pembrolizumab plus ipilimumab is not an approved regimen, it is hard to extrapolate that to our combination treatments that are approved. I think some clinicians might find that data valuable when making a frontline treatment decision on a patient who has PD-L1 high status. So a bit of a whirlwind tour, but I think there are still multiple factors that went into this guideline that are important to review when making treatment decisions for any one patient. Brittany Harvey: Absolutely. I think what you just mentioned in having that upfront molecular testing is really key for individualized patient care. And the evidence summaries that you provide in addition to the recommendations are really important for clinicians to be able to refer to as they are making decisions in their clinic. So then beyond those changes for first-line therapy, what is updated for second-line and subsequent therapies? Dr. Joshua Reuss: For second-line and subsequent therapies, we did see one new treatment recommendation join these ranks, and that was telisotuzumab vedotin. Telisotuzumab vedotin, quite a mouthful. That is an antibody-drug conjugate. I like to think of that as smart chemotherapy, targeted chemotherapy, where you are trying to utilize some aspect of a marker that is selectively expressed or overexpressed on the cancer surface to then shepherd in the anticancer molecule, a highly potent chemotherapeutic in the case of currently approved antibody-drug conjugates, to exert antitumor killing effect. So in this case, the antibody-drug conjugate telisotuzumab vedotin targets MET overexpression. So telisotuzumab is an antibody targeting MET, and that is conjugated to an MMAE highly potent chemotherapeutic payload called vedotin. So we know MET can be selectively expressed and overexpressed in non-small cell lung cancer in both driver mutation-positive and mutation-negative subsets. The data that led to this approval was from the phase II LUMINOSITY trial which evaluated telisotuzumab vedotin, or Teliso-V, in many subsets. But the subset that really showed promise and was expanded was the EGFR wild-type, non-squamous, non-small cell lung cancer population with MET overexpression. And so in 78 patients with high levels of expression, the response rate here was 34.6%, median progression-free survival of 5.5 months, and a median overall survival of 14.6 months. With an overall acceptable safety profile; grade 3 or higher adverse events, neuropathy was perhaps the most common at 7%, also increased ALT at 3.5%, and pneumonitis at 2.9%. Now this was phase II data that led to an accelerated approval. There is an ongoing phase III study randomizing patients with high expression to Teliso-V versus docetaxel. That is the phase III TeliMET study. But it is nice that we now have another option for patients, perhaps a more biomarker-directed option with, again, this MET overexpression. And again, it further reinforces the importance of molecular testing in patients with traditionally driver mutation-negative non-small cell lung cancer, whether that is upfront or at progression, and in particular utilizing immunohistochemistry to assess MET expression in these patients. And this does join another ADC that we had previously made an update in our recommendation, which is trastuzumab deruxtecan, which is approved for those patients with HER2-overexpressing non-small cell lung cancer. So just again to reiterate the importance of molecular testing in patients both at the outset of their treatment and upon progression on frontline therapy. Brittany Harvey: Definitely. It is great to have this new antibody-drug conjugate join the treatment options, and as you mentioned, very important in this case to have that molecular testing done at the outset and at progression. So then in your view, what should clinicians know as they implement this living guideline, and how do these changes impact patients with non-small cell lung cancer? Dr. Joshua Reuss: Because there are so many different regimens that one can consider for any one patient, I think it is easy to become overwhelmed and stress on, "Am I making the right choice for my patient?" And I think one of the key take home points is that in many cases, there is no one right regimen. And I think one has to weigh several factors. It is the treatment schedule. It is the toxicity profile. It is the molecular profile of the patient. It is the patient preference. You know, there are so many factors here. And I would like to draw the reader and viewer's attention to an important section of these guidelines, particularly the Patient and Clinician Communication section, where we have a box focused on discussion points between patients and clinicians, which I think focuses on several of the high-level points that one can emphasize in making these decisions, ranging on things from: what are the goals of the treatment? What are the risks and benefits to any one approach? What are comorbidities that should be factored in? Common concerns, toxicity management, clinical trial consideration. All of these factors that I think are incredibly important in making that frontline treatment decision and implementing a regimen that both the clinician and, more importantly, the patient feels comfortable with. Brittany Harvey: It is really important that there is shared decision-making in these scenarios. And I think that patient-clinician communication section can tease out some of those preferences from the patient end and talk through the risks and benefits of different regimens as well. As we mentioned at the top of this episode, this guideline is a living guideline and updated on an ongoing basis. So what is the panel examining and keeping an eye on for future updates to this guideline? Dr. Joshua Reuss: So I think there are a lot of exciting new therapies and more up-to-date trials that we are anxiously awaiting the results of on our committee, and I think the oncology community in general is awaiting the results of. When we will have these results, I think, is a bit of an open-ended question, but I can give some insight on several of the trials that our committee is really keeping a close eye on. One that we have mentioned for several guideline iterations is the ECOG-ACRIN INSIGNA trial. This is a phase III clinical trial comparing pembrolizumab versus pembrolizumab plus carboplatin and pemetrexed chemotherapy in PD-L1 positive, non-squamous, non-small cell lung cancer. We talk about there being different regimens that can be considered in PD-L1 positive and PD-L1 high subsets, namely immunotherapy alone or immunotherapy plus chemotherapy, but there is no direct head-to-head comparison here. So this trial hopefully will answer that question. It has now finished accrual. There are other very interesting molecules and trials. I think another interesting compound is ivonescimab. This is a PD-1/VEGF bispecific antibody that is currently approved in China as monotherapy in patients with PD-L1 positive non-small cell lung cancer based off of the HARMONi-2 trial, where the progression-free survival of this bispecific antibody, ivonescimab, appeared superior to pembrolizumab. And we are looking closely at ongoing trials to see if these results will be replicated in an ex-China population. And if so, I think it could have a real impact and change on our guidelines. Still other very interesting things. There are obviously confirmatory studies for antibody-drug conjugates, such as the TeliMET study that I alluded to earlier, and many promising antibody-drug conjugates, both bispecific and trispecific antibody-drug conjugates, that hopefully can inform practice. And then there are several unique subsets of populations that I think we now are utilizing data on to make decisions, but a lot of that is retrospective in small subsets where we do not have that prospective data. And there are several trials ongoing in some of these subsets to try to gain clarity on what regimen may be the best for patients. One example is the phase III TRITON trial, which is looking at comparing CTLA-4 containing regimen, particularly the POSEIDON regimen of durvalumab plus tremelimumab and chemotherapy, versus the KEYNOTE-189 regimen, which is pembrolizumab plus carboplatin and pemetrexed, in patients with non-squamous, non-small cell lung cancer that have alterations in either KRAS, KEAP1, and/or STK11. There is a lot of both preclinical and clinical data to suggest that patients with these alterations in STK11 and KEAP1 may be more resistant to a PD-1 based treatment approach, and perhaps the incorporation of CTLA-4 can lead to a more meaningful response in this unique subset. Obviously, that data, it is retrospective, it is in small subsets. And when you add in a CTLA-4 molecule, you are also introducing greater risk for toxicity. So this trial is going to be very important in elucidating: is there a benefit in that unique subset? Does that data that we see retrospectively in this small subset hold true when evaluated in a prospective fashion? So while our guideline, our most recent comprehensive panel update, may not have had a lot of new data in it that has influenced frontline treatment decision-making, I think the future is bright and there are a lot of novel studies and novel treatments on the horizon that will hopefully improve the outcomes for our patients. Brittany Harvey: Absolutely. We will look forward to the results of those ongoing trials to provide more options and particularly clarity for patients with non-small cell lung cancer and to inform this guideline and its many updates to come. 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. Reuss. Dr. Joshua Reuss: Thank you so much. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines App 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.  

We love to hear from our listeners. Send us a message. On this week's episode of the Business of Biotech, Brian Hilberdink, President of U.S. Human Pharma at Boehringer Ingelheim, returns to the show during the J.P. Morgan Healthcare Conference, and following his departure from LEO Pharma (see episode 164). Brian talks about new opportunities in obesity, the benefits of private ownership in funding early science, Boehringer's deal strategy, using AI to improve commercialization efforts, and the FDA's selection of zongertinib (in patients with HER2-mutant NSCLC) for the Commissioner's National Priority Voucher program.    Access this and hundreds of episodes of the Business of Biotech videocast under the Business of Biotech tab at lifescienceleader.com. Subscribe to our monthly Business of Biotech newsletter. Get in touch with guest and topic suggestions: ben.comer@lifescienceleader.comFind Ben Comer on LinkedIn: https://www.linkedin.com/in/bencomer/

In today's episode, the discussion features Adam Fox, MD, an assistant professor in the Department of Medicine at the College of Medicine at the Medical University of South Carolina in Charleston, and Cynthia A. Schandl, MD, PhD, medical director of clinical laboratories and director of the Division of Clinical Pathology in the College of Medicine at the Medical University of South Carolina, who examined the expanding role of biomarker testing and genomic profiling in non–small cell lung cancer (NSCLC) across disease stages

As part of IASLC's ongoing series of Lung Cancer Considered podcast episodes in world languages, Dr. Ece Cali moderates a discussion in Turkish with Dr. Irfan Çiçin and Dr. Fulden Yumuk. The episode is part of our Virtual Tumor Board series and focuses on immunotherapy for non-small cell lung cancer (NSCLC).

In our second episode of the "Perspectives" series, Dr. Paul Wheatley-Price chats with two guests, both with a depth of experience in ROS1+ lung cancer, a rare subtype of non-small cell lung cancer (NSCLC) which represents only about 1-2% of all lung cancer cases in Canada. Rev. Richard Reimer from Edmonton shares his story being diagnosed in 2009 with stage 4 lung cancer that was later identified as ROS1, and how he's been navigating life ever since. Dr. Geoffrey Liu is a Medical Oncologist at the Princess Margaret Cancer Center in Toronto and provides his clinical expertise on what is ROS1, how common is it, how does it get tested, and what the current treatment options are for those diagnosed with this rare subtype of lung cancer. This episode is dedicated to Richard's late beloved wife, Dana Rayment ❤️

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/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/YDH865. CME/MOC/AAPA/IPCE credit will be available until December 22, 2026.Taking the High Road in NSCLC: Navigating Through Immunotherapy-Based Treatments to Optimize Outcomes 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 independent educational grant from Regeneron Pharmaceuticals, 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/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/YDH865. CME/MOC/AAPA/IPCE credit will be available until December 22, 2026.Taking the High Road in NSCLC: Navigating Through Immunotherapy-Based Treatments to Optimize Outcomes 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 independent educational grant from Regeneron Pharmaceuticals, 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/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/YDH865. CME/MOC/AAPA/IPCE credit will be available until December 22, 2026.Taking the High Road in NSCLC: Navigating Through Immunotherapy-Based Treatments to Optimize Outcomes 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 independent educational grant from Regeneron Pharmaceuticals, 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/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/YDH865. CME/MOC/AAPA/IPCE credit will be available until December 22, 2026.Taking the High Road in NSCLC: Navigating Through Immunotherapy-Based Treatments to Optimize Outcomes 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 independent educational grant from Regeneron Pharmaceuticals, 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 information, and to apply for credit, please visit us at PeerView.com/YJT865. CME credit will be available until 30 December 2026.The Challenges of Choice in First-Line EGFRm NSCLC: Practical Guidance on Optimising Treatment Approaches 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 independent educational grant from AstraZeneca.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 information, and to apply for credit, please visit us at PeerView.com/YJT865. CME credit will be available until 30 December 2026.The Challenges of Choice in First-Line EGFRm NSCLC: Practical Guidance on Optimising Treatment Approaches 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 independent educational grant from AstraZeneca.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 information, and to apply for credit, please visit us at PeerView.com/YJT865. CME credit will be available until 30 December 2026.The Challenges of Choice in First-Line EGFRm NSCLC: Practical Guidance on Optimising Treatment Approaches 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 independent educational grant from AstraZeneca.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 information, and to apply for credit, please visit us at PeerView.com/YJT865. CME credit will be available until 30 December 2026.The Challenges of Choice in First-Line EGFRm NSCLC: Practical Guidance on Optimising Treatment Approaches 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 independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

The current landscape of testing for NSCLC is complex, with many new biomarkers emerging rapidly, more points during which testing is possible, and precision drug treatments available on the basis of findings from biomarker testing. While promising for patients, the result of this rapidly changing landscape is confusion from interdisciplinary care teams as to what testing is necessary and when, who in multidisciplinary care teams should be ordering new tests and when, and what workflows are necessary for labs. Host David Ritter, MA is joined by Dr. Ying-Chun Lo and Dr. Mamatha Chivuluka to discuss what things pathologists and lab professionals need to know about emerging biomarkers for NSCLC. In this conversation, the panel reflects on how NSCLC biomarker testing has evolved over the past decade, highlighting the shift from limited, sequential testing to guideline-recommended broad molecular profiling. Drs. Lo and Chivuluka explore the clinical relevance of emerging biomarkers such as HER2, TROP2, and HER3, and discuss how new targeted therapies are influencing testing strategies in real-world practice. They also examine practical considerations for laboratories, including platform selection across IHC, PCR, and NGS, approaches to tissue stewardship in small lung biopsies, and the growing leadership role of pathologists in multidisciplinary teams to ensure timely, guideline-concordant, and equitable access to biomarker testing for patients with NSCLC. 

As Barry Manilow's recent lung cancer diagnosis reminded us, a persistent cough, chest pain, shortness of breath may be more than just annoying symptoms. In this episode, we explain the signs you shouldn't ignore, what testing and treatment may look like, and how hope is still part of the story.  https://bit.ly/4szFIiaIn this Episode:02:21 - Tips for Longevity from People in their 90's - Naomi Rose & Physical Fitness04:48 - Avocado Salsa: Marriage of Guacamole and Pico de Gallo05:47 - Barry Manilow's Lung Cancer Diagnosis07:05 - Review of Lung Anatomy, Lung Cancer Overview, Differences between NSCLC and SCLC 09:32 - What Increases Our Risk of Lung Cancer?10:35 - Lung Cancer Signs and Symptoms to Watch For12:49 - Treatment of Lung Cancer - Reasons for Hope15:46 - Cancer Survivorship: How to Lower Your Risk of Cancer Returning and Signs not to Ignore18:57 - Discussion with Charlie: Historical Smoking, Persistent Cough24:04 - 27 y.o. Alexa Bekkerus Self-Written Obituary - How She Found Peace Dying with Metastatic Breast Cancer29:21 - OutroSupport the showGet show notes and resources at our website: every1dies.org. Facebook | Instagram | YouTube | mail@every1dies.org

Drs. Herzberg and Yu continue their discussion on emerging clinical data presented at ESMO and WCLC 2025. They highlight recent advancements in HER2-targeted therapies for NSCLC and review new HER2-targeted therapies, international study results, and the promise of evolving targeted approaches for HER2-altered lung cancer.

In today's episode, we sat down with Julia Rotow, MD, and Gavitt Woodard, MD, to talk through recent updates to the perioperative non–small cell lung cancer treatment paradigm. 

Are you up to date on the evolving treatment landscape for HER2-mutated non-small cell lung cancer (NSCLC)? Do you know the role of novel targeted therapies? Credit available for this activity expires: 12/24/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/precision-oncology-her2-mutated-nsclc-strategies-today-and-2025a100105r?ecd=bdc_podcast_libsyn_mscpedu

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/JZU865. CME/MOC/NCPD/AAPA/IPCE credit will be available until December 18, 2026.Addressing un-MET Needs in NSCLC: Elevating MET-Targeting Options for Patients With a Poor Prognosis In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and MET Crusaders. 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 independent educational grant from AbbVie.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/JZU865. CME/MOC/NCPD/AAPA/IPCE credit will be available until December 18, 2026.Addressing un-MET Needs in NSCLC: Elevating MET-Targeting Options for Patients With a Poor Prognosis In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and MET Crusaders. 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 independent educational grant from AbbVie.Disclosure information is available at the beginning of the video presentation.

Drs. Herzberg and Yu explore emerging clinical data from the 2025 meetings of the European Society For Medical Oncology (ESMO) and World Conference on Lung Cancer (WCLC), highlighting recent advancements in HER2-targeted therapies for NSCLC. Their discussion focuses on new drugs (eg, zongertinib and trastuzumab deruxtecan), their efficacy and safety profiles, and the potential for treating HER2 mutations and overexpression.

In this episode, Dr John Heymach and Dr Solange Peters discuss key data presented at the IASLC World Conference on Lung Cancer including first-line maintenance in ES-SCLC (IMforte and DeLLphi-303 trials) and targeted treatment for NSCLC (FLAURA2, Beamion LUNG-1, and ARROS-1 trials).Presenters:John Heymach, MD, PhDChair and ProfessorDepartment of Thoracic/Head and Neck Medical OncologyRuth Legett Jones Distinguished ChairMD Anderson Cancer CenterHouston, TexasSolange Peters, MD, PhD Professor and Director of Medical OncologyDepartment of OncologyUniversity Hospital of LausanneLausanne, SwitzerlandContent based on an online CME program supported by independent educational grants from Boehringer Ingelheim Pharmaceuticals, Inc. and Jazz Pharmaceuticals, Inc.Link to full program: https://bit.ly/3L1eksIGet access to all of our new podcasts by subscribing to the CCO Infectious Disease Podcast on Apple Podcasts, YouTube Music, or Spotify. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

Ready to close the gap in HER2-mutant NSCLC care? Join Memorial Sloan Kettering experts Helena A. Yu, MD, and Maria Arcila, MD, for a live webinar on optimizing HER2 testing and integrating the latest targeted therapies into your practice. They'll walk through how to improve detection and ensure your patients are getting the most effective, up-to-date treatments available. You can catch the live session on either of these dates: Wednesday, January 8 at 5:00 pm ET: https://bit.ly/4iZxnA0 Monday, January 26 at 5:00 pm ET: https://bit.ly/4qALw9J

In today's episode, we had the pleasure of speaking with Edward S. Kim, MD, MBA; and Jyoti Malhotra, MD, MPH, about the promise of IB6 as a therapeutic target in non–small cell lung cancer (NSCLC) management. Dr Kim is physician-in-chief of City of Hope Orange County, vice physician-in-chief of the City of Hope National Medical Center, and a professor in the Department of Medical Oncology & Therapeutics Research at City of Hope in Irvine, California. Dr Malhotra is interim division chief of Thoracic Medical Oncology, an associate professor in the Department of Medical Oncology & Therapeutics Research, and the director of Thoracic Medical Oncology at City of Hope. In our exclusive interview, Drs Kim and Malhotra discussed factors that make IB6 unique compared with other NSCLC biomarkers, the prevalence of IB6 expression among patients with lung cancer, and the rationale for investigating sigvotatug vedotin (formerly SGN-B6A) vs docetaxel in patients with previously treated NSCLC in the phase 3 Be6A Lung-01 trial (NCT06012435). 

Please visit answersincme.com/860/99120473-replay to participate, download slides and supporting materials, complete the post test, and get a certificate. In this activity, experts in oncology discuss the latest advances in HER2- and TROP2-directed ADCs for the management of advanced NSCLC, and how these approved and emerging ADCs may impact patients' treatment algorithms. Upon completion of this activity, participants should be better able to: Identify the rationale for targeting HER2 and TROP2 in the treatment of non-small cell lung cancer (NSCLC; Discuss the clinical impact of approved and emerging HER2- and TROP2-directed antibody-drug conjugates (ADCs) in NSCLC; and Formulate evidence-based strategies for the individualized management of patients with NSCLC using HER2- and TROP2-directed ADCs.

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

Featuring perspectives from Dr Justin F Gainor, Dr Corey J Langer and Dr Misty Dawn Shields, moderated by Dr Stephen "Fred" Divers, including the following topics:  Introduction (0:00) Targeted Therapy for Non-Small Cell Lung Cancer (NSCLC) — Dr Gainor, MD (5:32) Case: A woman in her mid 60s with ALK-mutant metastatic adenocarcinoma of the lung (PD-L1 TPS 70%) — Zanetta S Lamar, MD (17:59) Case: A woman in her mid 80s with EGFR exon 19-deleted adenocarcinoma of the lung with recurrence after 4 years of osimertinib — Jennifer Yannucci, MD (27:53) Case: A woman in her late 60s with HER2-mutant metastatic adenocarcinoma of the lung — Brian P Mulherin, MD (39:41) Case: A man in his early 70s with locally recurrent squamous cell carcinoma of the lung and a MET exon 14 skipping mutation — Sean Warsch, MD (46:39) Case: A woman in her early 70s with ROS1-mutant metastatic adenocarcinoma of the lung that responds to entrectinib and then to pembrolizumab/carboplatin/pemetrexed administered upon disease progression — Dr Yannucci (52:44) Nontargeted Therapy for NSCLC; Small Cell Lung Cancer — Dr Langer (58:16) Neoadjuvant, Perioperative and Adjuvant Anti-PD-1/PD-L1 Antibody-Based Approaches for Patients with Localized NSCLC — Dr Shields (1:14:14) Case: A man in his mid 60s with localized adenocarcinoma of the lung who receives neoadjuvant cisplatin/pemetrexed/pembrolizumab and achieves a pathologic complete response — Dr Mulherin (1:23:19) Case: A man in his early 60s with metastatic mixed adenosquamous NSCLC (PD-L1 TPS 50%) — Sunil Babu, MD (1:30:04) Case: A man in his late 50s diagnosed with extensive-stage small cell lung cancer who receives carboplatin/etoposide/durvalumab — Dr Warsch (1:34:07) CE information and select publications

Featuring an interview with Dr John V Heymach, including the following topics: Differentiating factors among various HER2 alterations in non-small cell lung cancer (NSCLC) (0:00) Activity of targeted agents across HER2 alterations in NSCLC (4:06) Available data with zongertinib and sevabertinib for HER2-mutant NSCLC (20:39) Case: A man in his late 40s with HER2-mutant NSCLC receives multiple lines of therapy, including trastuzumab deruxtecan (T-DXd) and zongertinib (29:23) Case: A woman in her mid 50s with HER2-mutant NSCLC receives zongertinib with durable response (34:23) Case: A woman in her late 50s with HER2-mutant NSCLC receives multiple lines of therapy, including sevabertinib and T-DXd (39:53) Investigational approaches in HER2-mutant NSCLC (46:31) CME information and select publications

Featuring a slide presentation and related discussion from Dr John V Heymach, including the following topics: Overview of the biology and treatment landscape of HER2-mutant non-small cell lung cancer (NSCLC) (0:00) Datasets evaluating trastuzumab deruxtecan for HER2-mutant NSCLC (5:03) Clinical data with zongertinib for HER2-mutant NSCLC (6:35) Emerging data with sevabertinib for HER2-mutant NSCLC (14:41) Other investigational strategies being evaluated for HER2-mutant NSCLC (19:10) Summary of the current and future treatment landscape of HER2-mutant NSCLC (21:52) CME information and select publications

In today's episode, we had the pleasure of speaking with Catherine Shu, MD, about the use of tepotinib (Tepmetko) in patients with non–small cell lung cancer harboring MET exon 14 skipping mutations. Dr Shu is the Price Family Associate Professor of Medicine and the clinical director of the Thoracic Medical Oncology Service at the Columbia University Herbert Irving Comprehensive Cancer Center in New York, New York.  In our exclusive interview, Dr Shu discussed updated data from the phase 2 VISION trial (NCT02864992) that investigated tepotinib in this population, the notable efficacy of this agent in treatment-naive patients, and considerations for managing and mitigating the adverse effects associated with this therapy. 

"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

ABOUT THIS EPISODE Who is a pharmacist, and how are they involved in the care of neuroendocrine cancer patients? In this episode, Dr. Amanda Cass, a clinical pharmacist in the Thoracic Oncology Clinic at Vanderbilt Medical Center, explains the unique role pharmacists play—why they're sometimes called “doctor,” how they support patients starting treatments such as cabozantinib and CAPTEM, and practical tips for staying organized, managing side effects, and navigating medication costs. TOP TEN QUESTIONS Getting to Know the Pharmacist1. What exactly does a pharmacist do, and what training do they go through?2. Why are pharmacists sometimes called “doctor,” and how is that different from a physician? 3. What role does a pharmacist play on the cancer care team? 4. How are pharmacists involved in caring for neuroendocrine cancer patients, both directly and behind the scenes?How Pharmacists Support Treatment5. How can a pharmacist help when someone is starting a new treatment for neuroendocrine cancer? Walk us through an example with Cabozantinib: how do you guide patients in understanding it, taking it, and managing side effects?6. Walk us through another example with CAPTEM (capecitabine and temozolomide): how do you guide patients in understanding it, taking it, and managing side effects?Practical Tips for Patients7. What are some simple ways to stay organized, like keeping a medication list or symptom journal? 8. What practical tips do you share with patients about tracking and managing side effects at home?Access and Communication9. Who can patients talk to about medication costs or financial assistance?10. How does someone find a pharmacist to talk to, and is it important to find one with neuroendocrine cancer experience?ABOUT AMANDA CASSDr. Cass is a clinical pharmacist in the Thoracic Oncology Clinic at Vanderbilt University Medical Center. She received her Doctorate of Pharmacy from the University of Kentucky College of Pharmacy in 2016 and subsequently completed her Pharmacy Practice Residency at Grady Health System and became a Board Certified Pharmacotherapy Specialist in 2017. In 2018, she completed her Oncology Pharmacy Residency at the University of North Carolina Medical Center.Dr. Cass's previous research interests included opioid use in non-metastatic cancer patients after curative treatment and albumin effects on oxaliplatin related toxicities. Her current areas of interest are molecular mutations and use of targeted therapies in NSCLC, immunotherapy in SCLC, and global oncology care.Dr. Cass is the preceptor for the Outpatient Thoracic Oncology Rotation.For more information, visit NCF.net/podcast/50For more information, visit NCF.net.

We are back with lots of OncoPharm updates: 1. The belantamab mafodotin REMS program details are available....and it's a lot. How will belantamab mafodin-regimens be used with the upcoming MAJESTIC-3 data of teclistamab-daratumumab? 2. The capecitabine label is updated and calls for pre-treatment DPYD testing 3. Daratumumab gets an FDA approval for high-risk smoldering myeloma based on the AQUILA study Critique of AQUILA: https://doi.org/10.1093/oncolo/oyaf216 4. A pertuzumab biosimilar (Poherdy) is approved 5. Epcoritamab nets regular approval and a new indication with lenalidomide/rituximab (RR) for Follicular Lymphoma 6. Ziftomenib, a new menin inhibitor, is approved for NPM1 relapsed/refractory AML 7. Sevabertinib, a new HER2 inhibiting TKI, is approved for ERBB2 mutated NSCLC, with evidence of activity in patients previously treated with HER2-antibody-drug conjugates 8. Expected FDA approvals for durvalumab + FLOT in preoperative gastric/GEJ cancer; neoadjuvant pembrolizumb + enforumab vedotin in bladder cancer (non-cisplatin eligible), and tarlatamab regular approval for small cell lung cancer 9. Happy Thanksgiving!

When cancer spreads to the brain, what is the best approach: immediate local treatment or systemic immunotherapy first? Part two of the 2025 NSCLC Creator Weekend™ series focuses on a complex case involving a 75-year-old woman with a history of breast malignancy, presenting with new dyspnea and a large mass in the left lower lobe. --- This podcast is supported by an educational grant from Johnson & Johnson and Varian. --- SYNPOSIS Our mock tumor board consists of surgeons, medical oncologists, and radiation oncologists to deliberate and determine the best treatment plan. The specialists explore diagnostic and treatment options, including neoadjuvant chemoimmunotherapy, invasive mediastinal staging, and the potential for surgical resection or radiation therapy. --- TIMESTAMPS 00:00 - Introduction05:01 - Approach to Isolated Brain Metastasis09:09 - Radiation Therapy Considerations12:06 - Imaging and Follow-Up Strategies14:39 - Resectability and Surgical Decisions19:10 - Conclusion --- RESOURCES PACIFIC Clinical Trialhttps://www.nejm.org/doi/full/10.1056/NEJMoa1709937

"It's critical to identify those mutations found that are driving the cancer's growth and guide the personalized treatment based on those results. And important to remember, too, early testing is crucial for patients with non-small cell lung cancer (NSCLC). In studies, it has been found to be associated with improved survival outcomes and reduced mortality," ONS member Vicki Doctor, MS, BSN, BSW, RN, OCN®, precision medicine director at the City of Hope Atlanta, GA, Chicago, IL, and Phoenix, AZ, locations, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about the oncology nurse's role in NSCLC biomarker testing. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  This podcast is sponsored by Lilly Oncology 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 363: Lung Cancer Treatment Considerations for Nurses Episode 359: Lung Cancer Screening, Early Detection, and Disparities Episode 238: Cancer Genomics for Every Oncology Nurse Episode 157: Biomarker Testing Improves Outcomes for Patients With Non-Small Cell Lung Cancer ONS Voice articles: Non-Small Cell Lung Cancer Prevention, Screening, Diagnosis, Treatment, Side Effects, and Survivorship Only a Third of Patients With Advanced Cancer Get Biomarker Testing, Limiting Use of Potentially Effective Precision Therapies Precision Medicine in Lung Cancer: How Comprehensive Testing Optimizes Patient Outcomes Targeted Therapies Are Transforming the Treatment of Non-Small Cell Lung Cancer ONS book: Guide to Cancer Immunotherapy (second edition) ONS course: Genomic Foundations for Precision Oncology Clinical Journal of Oncology Nursing article: Using Nurse Navigators to Improve Timeliness of Biomarker Testing for Non-Small Cell Lung Cancer Oncology Nursing Forum article: Precision Medicine Testing and Disparities in Health Care for Individuals With Non-Small Cell Lung Cancer: A Narrative Review Other ONS resources: Best Practices for Biomarker Testing in Non-Small Cell Lung Cancer: A Case Study Genomics and Precision Oncology Learning Library Genomics Case Study: Precision Medicine in the Setting of Metastatic Non-Small Cell Lung Cancer Biomarker Database (refine by non-small cell lung cancer) Genomic Biomarkers Huddle Card Targeted Therapy Huddle Card National Comprehensive Cancer Network homepage 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 "These biomarkers are used to provide information about cancer's characteristics or behavior. In oncology precision medicine specifically, molecular tests can help with diagnosing a cancer that is maybe an unknown primary. It can help with monitoring response to therapy, detect recurrence of disease before other tests can find that, predict prognosis or how aggressive the cancer may be, and guide treatment decisions for targeted therapies." TS 3:14 "Some of the key biomarkers recommended by the National Comprehensive Cancer Network (NCCN) to be tested in patients who have NSCLC are EGFR, ALK, KRAS, BRAF, MET exon 14 skipping mutation, HER2 which is a protein expression from an ErbB protein, PD-L1 which is a protein expression that's used to guide immunotherapy choices, and then finally there are three fusions: ROS1, RET, and NTRK. [These] are pretty rare but really important to be tested for in patients who have NSCLC." TS 3:46 "Another important challenge for nurses related to this topic is that these results may not reveal a targeted mutation for the patient and that could be very disappointing. So, being able to provide that emotional support to a patient if they have that result … you can actually reinforce with them that if [they] go onto another treatment that the physician decides to put [them] on, the tumor can change. New pathogenic variants can develop based on the treatment that they're getting, and another test can be done. And maybe at that time—a new biomarker that could be targeted—we'd be seeing on the new test." TS 7:32  "Another circumstance we didn't talk about yet is that maybe the result came back saying that the quality was not sufficient. And sometimes that happens, but that doesn't mean that we're at the end of the road, necessarily. So, you could explain to the patient that that may mean that possibly, a new biopsy would be ordered by the physician. Or if a new biopsy or another tissue sample is not available, then maybe the physician would pivot to sending a blood specimen for the molecular testing. So that would definitely be a way [nurses] could support their patients." TS 11:52 "In the case of patients with NSCLC, early testing is so important. So, advocating for that prompt biomarker testing to be done, making sure that it's comprehensive, that it's actually looking for all of those—I think it was 12 biomarkers—that I mentioned earlier. That this testing is done as soon as possible after diagnosis or progression. Something that I talk about all the time—personalized care, precision medicine—really matters. So, tailoring treatments for patients based on the biology of the tumor that's driving the cancer's growth is really crucial if you're going to be working as an oncology nurse. Another crucial thing, because it's changing so quickly, is to stay informed." TS 16:23

Welcome to the Oncology Brothers podcast! In this episode, we dive into the management of ROS1 fusion positive non-small cell lung cancer (NSCLC) and explore the various tyrosine kinase inhibitors (TKIs) available for this rare subset of patients. Join us along with special guest Dr. Estelamari Rodriguez, a thoracic medical oncologist from Sylvester Comprehensive Cancer Center, as we discussed: • The importance of comprehensive next-generation sequencing (NGS) in management of NSCLC. • A detailed overview of ROS1 TKIs, including crizotinib, repotrectinib, entrectinib, taletrectinib. • Common side effects associated with these agents, such as fatigue, dizziness, edema, and liver toxicity. • Clinical pearls for managing adverse events and optimizing patient care. • The significance of patient education and regular follow-ups in ensuring treatment adherence and safety. Whether you're a healthcare professional or someone interested in oncology, this episode provides valuable insights into the practical aspects of treating ROS1 fusion positive NSCLC. 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 check out our other ToxCheck episodes, conference highlights, and treatment algorithms. Subscribe for more discussions on bridging the gap between academic research and community practice! #ROS1 #NSCLC #TKIs #Crizotinib #Repotrectinib #Entrectinib #Taletrectinib #TargetedTherapy #OncologyBrothers #LungCancer