Podcasts about nsclc

Our Landmarks of OncoPharm series returns to discuss PARAMOUNT, a landmark study that helped solidify the role of maintenance pemetrexed in NSCLC.

In today's episode, we had the pleasure of speaking with Stephen Liu, MD, about the use of tepotinib (Tepmetko) in patients with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations. Dr Liu is an associate professor of medicine at Georgetown University, as well as the director of Thoracic Oncology and head of Developmental Therapeutics at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. In our exclusive interview, Dr Liu discussed key efficacy and safety findings from the phase 2 VISION trial (NCT02864992) that led to the FDA approval of tepotinib for this indication; the comparable response rates seen between tissue and liquid biopsy results, as well as across NSCLC treatment lines; and the importance of early biomarker testing, including RNA sequencing, to identify actionable mutations and optimize treatment.

Please visit answersincme.com/860/MED-ONC-03349-replay to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, experts discuss how the latest data for first-line immunotherapy-based regimens informs personalized approaches for advanced NSCLC and how to elevate care through patient advocate–centered approaches. Upon completion of this activity, participants should be better able to: Differentiate the clinical profiles of NCCN-preferred first-line immunotherapy-based regimens for advanced NSCLC based on the latest data for disease with no actionable mutations and PD-L1 expression 50% or greater; Identify how first-line treatment selection varies for different patient subpopulations with advanced NSCLC with no actionable mutations and PD-L1 expression 50% or greater; and Apply patient-centered strategies to optimize the integration of immunotherapy-based regimens into first-line treatment plans of patients with advanced NSCLC with no actionable mutations and PD-L1 expression 50% or greater.

In today's episode, we had the pleasure of speaking with Alexander Drilon, MD, about the phase 1/2 ARROS-1 trial (NCT05118789) investigating zidesamtinib (NVL-520) in TKI-pretreated patients with advanced ROS1-positive non–small cell lung cancer (NSCLC). Dr Drilon is chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center in New York, New York. In our exclusive interview, Dr Drilon discussed the efficacy data and implications of the ARROS-1 trial, highlighted the unique mechanism of action of zidesamtinib, noted the high central nervous system (CNS) response rates and favorable safety profile associated with the agent, and emphasized the potential for zidesamtinib to become a standard first-line therapy in the NSCLC treatment paradigm, especially for patients with prior TKI resistance or CNS disease.

Moderator: Gerard A. Silvestri MD, MS, Master FCCP Guest: Jessica S. Donington, MD, MSCR Guest: Mariam Alexander, MD, PhD Guest: Anurag Singh, MD Effective care for non-small cell lung cancer (NSCLC) now depends on early molecular testing and coordinated input from a variety of specialties. Dr. Gerard Silvestri sits down with Drs. Jessica Donington, Mariam Alexander, and Anurag Singh to review why multidisciplinary integration is critical to avoid treatment delays, ensure appropriate therapy selection, and ultimately improve patient outcomes. Dr. Silvestri is a pulmonologist and the Hillenbrand Professor of Thoracic Oncology at the Medical University of South Carolina; Dr. Donington is a Professor of Surgery and Chief of the Section of Thoracic Surgery at the University of Chicago; Dr. Alexander is an Assistant Professor of Medicine and Medical Oncology at the Medical University of South Carolina; and Dr. Singh is the Director of Radiation Research, Director of the Head and Neck and Lymphoma Radiation Services, and the Associate Dean of Graduate Medical Education in Radiation Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York. This program is produced in partnership with the American College of Chest Physicians and is sponsored by AstraZeneca.

New survival data from the FLAURA2 and MARIPOSA trials represent “a massive advance for our patients” in terms of frontline treatment for EGFR-mutated non-small cell lung cancer says Sandip P. Patel, MD, professor of medicine at the University of California San Diego. However, the findings have led to new questions about sequencing. “Just like in chess, when you make a move, you're restricted in the moves that you can make afterward,” he explains to Robert A. Figlin, MD, the interim director of Cedars-Sinai Cancer in Los Angeles and Steven Spielberg Family Chair. Discussions have become “much more nuanced,” and “thinking about the patient holistically becomes even more important in the setting of all these excellent treatment options for our patients,” Dr. Patel shares. Dr. Patel reported scientific advisory income from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Certis, Eli Lilly, Jazz, Genentech, Illumina, Merck, Pfizer, Natera, and Tempus. Dr. Figlin reported various financial relationships.

Moderator: Gerard A. Silvestri MD, MS, Master FCCP Guest: Jessica S. Donington, MD, MSCR Guest: Mariam Alexander, MD, PhD Guest: Anurag Singh, MD Recent data from ASCO and ASTRO 2025 are redefining standards of care for resectable non-small cell lung cancer (NSCLC). Drs. Gerard Silvestri, Mariam Alexander, Anurag Singh, and Jessica Donington review these updates on the importance of molecular testing, careful surgical selection, and multidisciplinary planning to optimize personalized treatment pathways. Dr. Silvestri is a pulmonologist and the Hillenbrand Professor of Thoracic Oncology at the Medical University of South Carolina; Dr. Alexander is an Assistant Professor of Medical Oncology at the Medical University of South Carolina; Dr. Singh is the Director of Radiation Research, Director of Head and Neck and Lymphoma Radiation Services, and the Associate Dean of Graduate Medical Education in Radiation Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York; and Dr. Donington is a Professor of Surgery and Chief of the Section of Thoracic Surgery at the University of Chicago. This program is produced in partnership with the American College of Chest Physicians and is sponsored by AstraZeneca.

To Josh's immense displeasure, our series on genitourinary cancer is done. For now, at least. In this episode, Michael and Josh step into the heavy shadow of non-small cell lung cancer, the most common cause of cancer death in Australia. However, there is hope and new developments in the early-disease space that could significantly improve outcomes. Studies discussed in this episodeCheckmate 816neoADAURAFor more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have access to the episode at the same time you do and have no editorial control over the content. Hosted on Acast. See acast.com/privacy for more information.

Featuring an interview with Dr Jacob Sands, including the following topics: Management of Adverse Events of Special Interest Associated with Datopotamab Deruxtecan (Dato-DXd) (0:00) Heist RS et al. Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan. Cancer Treat Rev 2024;125:102720. Abstract  Sands J et al. Analysis of drug-related interstitial lung disease (ILD) in patients (pts) treated with datopotamab deruxtecan (Dato-DXd). ASCO 2024;Abstract 8623. Intracranial Efficacy of Dato-DXd for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with Actionable Genomic Alterations in the TROPION-Lung05 Study (7:23) Lisberg A et al. Intracranial efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously treated advanced/metastatic non-small cell lung cancer (a/m NSCLC) with actionable genomic alterations (AGA): Results from TROPION-Lung05. ASCO 2024;Abstract 8593.  Clinical Evidence Supporting the Combination of Dato-DXd with Immune Checkpoint Inhibition for Advanced NSCLC (12:12) Bessede A et al. TROP2 is associated with primary resistance to immune checkpoint inhibition in patients with advanced non-small cell lung cancer. Clin Cancer Res 2024;30(4):779-85. Abstract Levy BP et al. TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC). ASCO 2025;Abstract 8501. Waqar SN et al. First-line (1L) datopotamab deruxtecan (Dato-DXd) + rilvegostomig in advanced or metastatic non-small cell lung cancer (a/mNSCLC): Results from TROPION-Lung04 (cohort 5). ASCO 2025;Abstract 8521. Current and Future Development of Antibody-Drug Conjugates in the Treatment of Lung Cancer (17:11) Tawfiq RK et al. Targeting lung cancer with precision: The ADC therapeutic revolution. Curr Oncol Rep 2025;27(6):669-86. Abstract CME information and select publications

The 2025 World Conference on Lung Cancer just concluded, and there are several notable updates concerning treatment of EGFR-mutated NSCLC. 1. The COMPEL study tries to find the value of continuing osimertinib (with the addition of chemotherapy) after progression on osimertinib. The results are, well, compelling! 2/3. We now have updates on the OS benefits of osimertinib + chemotherapy (FLAURA2) and amivantamab + lazertinib (MARIPOSA) compared to osimertinib monotherapy in initial treatment of metastatic disease. 4. NEOADAURA tries to determine if neoadjuvant osimertinib has value, but longer follow-up will be needed to assess this practice.

Are you up to date with therapy strategies for ALK translocation and EGFR mutation–positive non-small cell lung cancer? Credit available for this activity expires: 9/10/26 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1002896?ecd=bdc_podcast_libsyn_mscpedu

Natasha Leighl, MD, MMSc, FRCPC, FASCO - Targeting Improved Outcomes in ALK-Positive NSCLC: A Canadian Clinician's Guide to Optimizing Outcomes Across the Spectrum of Disease

Please visit answersincme.com/860/98320325-replay to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, experts in oncology discuss the evolving role of HER2-targeted antibody–drug conjugates (ADCs) and how to integrate them into clinical practice. Upon completion of this activity, participants should be better able to: Recognize the role of biomarker testing for the management of HER2-overexpressing NSCLC; Evaluate the clinical significance of new and emerging HER2-targeting ADCs for HER2-overexpressing NSCLC; and Apply strategies to optimize the use of HER2 targeting ADCs in patients with NSCLC.

In today's episode, we had the pleasure of speaking with Balazs Halmos, MD, MS, about the phase 2 VISION trial (NCT02864992) evaluating tepotinib (Tepmetko) in patients with MET exon 14 skipping mutation–positive non–small cell lung cancer (NSCLC). Dr Halmos is a professor in the Department of Oncology (Medical Oncology) and the Department of Medicine (Oncology and Hematology), director of Thoracic Oncology, and associate director of Clinical Science at Montefiore Einstein Comprehensive Cancer Center in Bronx, New York. In our exclusive interview, Halmos discussed the rationale and design of the VISION trial, the significance of MET exon 14 skipping mutations as a distinct oncogenic driver, and the clinical utility of tepotinib, which is a selective MET TKI. He reviewed the trial's efficacy results, which demonstrated consistent response rates across lines of therapy and diagnostic methods, as well as tolerability findings that highlighted the importance of monitoring and managing MET-related adverse effects. Dr Halmos also reflected on subgroup analyses from the trial, noting the agent's activity across treatment settings, particularly in older patients and those with central nervous system involvement. Additionally, Halmos underscored the critical role of comprehensive biomarker testing in NSCLC, highlighting how parallel tissue- and circulating tumor DNA–based testing can optimize timely identification of actionable alterations and ensure patients receive the most effective frontline therapy. He also discussed practical considerations for dose selection and modifications with tepotinib, offering insights into strategies for maximizing treatment benefit and maintaining patient quality of life.

In this special WCLC 2025 episode of Lung Cancer Considered, hosts Dr. Narjust Florez and Dr. Stephen Liu discuss highlights from the conference. Dr. Susan Scott discusses EGFR mutant NSCLC and results from PALOMA-2 and subcutaneous amivantamab. Dr. Wenfeng Fang discusses Iza-Bren (BL-D01D1), a first-in-class EGFR x HER-3 biospecific ADC linked to a novel topoisomerase I inhibitor payload, with promising preliminary activity in EGFR positive previously treated NSCLC. Dr. Biagio Ricciuti shares his insights from WCLC 2025, including the FLAURA-2 OS readout, the HARMONi trial in EGFR positive NSCLC, and his research in the use of immunotherapy in early-stage lung cancer.

JCO fellow Dr. Ece Cali speaks with JCO Associate Editor Dr. Thomas E. Stinchcombe to discuss the JCO article "Phase 2 Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small-Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B)", that was simultaneously released at the IASLC 2025 World Conference on Lung Cancer. TRANSCRIPT Dr. Ece Cali: Hello, and welcome to our series where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's most important oncology meetings. I am your host, Dr. Ece Cali, JCO editorial fellow, and I am joined by Dr. Tom Stinchcombe, JCO associate editor, to discuss the Journal of Clinical Oncology article and 2025 World Conference on Lung Cancer abstract presentation, “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non–Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.” The WU-KONG1B trial is a multinational, phase II study that investigated the efficacy and safety of different doses of sunvozertinib in patients with metastatic non-small cell lung cancer and EGFR exon 20 insertion mutations after progression on platinum based chemotherapy. Tom, before we dive into the results, could you walk us through the rationale for this study, and how does it fit into the current treatment options for patients with EGFR exon 20 insertion? Dr. Tom Stinchcombe: Thank you, Dr. Cali. I think the clinical context is always important. We have known that EGFR exon 20 insertions exist and that they are resistant to our currently available EGFR tyrosine kinase inhibitors, and I think there have been attempts in the past to develop a tyrosine kinase inhibitor, but there is a very narrow therapeutic window between the dose you need to inhibit the EGFR mutation in the cancer and the EGFR receptor on normal tissues, most notably the mucosa, the gut, and the skin. And so, our previous attempts have failed largely because the dose required was not tolerable for patients and they could not really stay on the drug for a long time or they were not very active. And so, I think there was a real desire to develop an EGFR tyrosine kinase inhibitor, and then, historically, the standard had been a platinum based doublet as the standard of care. And more recently, platinum based doublet with amivantamab has proven to be superior to platinum based chemotherapy alone. I think the context is also important that amivantamab is not necessarily available in all the countries, and so, there are patients who do not have access to amivantamab. Going to the rationale, I think that this drug had shown preliminary promise of having activity but without that being encumbered by those EGFR wild type toxicities, and, therefore, it was really explored in this larger study. Dr. Ece Cali: And what are some key findings from this trial? Dr. Tom Stinchcombe: So, I think that we should look at the study design. It is a little quirky, for lack of a better term, in that there is a randomization to 200 versus 300 mg, and then, there was a nonrandomized cohort of 300 mg. So, when you look at the study, if you are a purist, you will just look at the randomized patients. If you are sort of an aggregator, you look at all patients. So, it shows reporting on three cohorts, but I think the key findings are that the 200 mg and the 300 mg treatments had similar toxicities in terms of response rate, duration of response, and progression free survival. And as you know going through the review, there was a lot of queries from the reviewers as to which would be the preferred dose, and to me, I think this really illustrates a dose finding component to a trial design because there is a lot of debate about what the minimal effective dose is or the optimal dose. And in this case, having the two dose cohorts did provide us some valuable efficacy and toxicity information. And then, when I look at the study, I want to make sure it reflects my patient population, and about a quarter of patients had brain metastases, and about 15% had previous amivantamab, and about 5% to 10% had another EGFR tyrosine kinase inhibitor. Dr. Ece Cali: And what is the objective response rate and the duration of response? These are pretty good numbers for this patient population. Dr. Tom Stinchcombe: In the 200 mg cohort, it was about 46%. The duration of response was around 11 months, and the PFS was around 8 months. The 300 mg cohort was 46%, duration of response 9.8, and the median PFS is 6.9 months, and I think that this is greater activity than we have seen with our previous attempts at EGFR tyrosine kinase inhibitors. Dr. Ece Cali: And based on these data, FDA granted accelerated approval for sunvozertinib very recently at 200 mg once daily dosing in this setting. So, that is a major step forward for our patients. Dr. Stinchcombe, how does this impact your clinical practice, and what side effects should oncologists be watching for if they prescribe this medication? Dr. Tom Stinchcombe: So, I think it was very interesting that they chose the 200 mg dose, which I think was more tolerable, and when we kind of look at this, there still was a rate of diarrhea, all grade, rash, paronychia, which are the EGFR related toxicities. There can be some decreased appetite, stomatitis, and then, it can lead to some lab abnormalities, like increased CPK and creatinine that physicians have to be aware of. You know, how it will affect my practice is that all these patients had received a platinum based chemotherapy as the first line therapy. I think that this would become my preferred second line therapy for patients outside the context of a trial because of the activity and the tolerability. Dr. Ece Cali: And lastly, several other tyrosine kinase inhibitors are being evaluated for EGFR exon 20 insertion, including in the frontline setting. So, what are some of the outstanding questions in this space, and what data should our listeners keep an eye on moving forward? Dr. Tom Stinchcombe: I think you are right that now, there is going to be another EGFR tyrosine kinase that may become available in the next year, and there is another drug, furmonertinib, that is being investigated. I think, for the clinical question, is, well, can we move these into the first line setting? And actually, the development path has two ways of doing this. There is EGFR tyrosine kinase compared to platinum based chemotherapy, and then, platinum based chemotherapy with an EGFR tyrosine kinase versus platinum based chemotherapy, and both have their merits and strengths. And so, I think it is going to be very interesting as we see if those first line trials, one, can they be demonstrated to be superior to platinum based chemotherapy, and then by what magnitude and what the side effects are. But I think we are hoping that in the next couple of years, we will have an additional first line option for our patients. Dr. Ece Cali: Yeah, it is always great to have more options for our patients. Thank you, Dr. Stinchcombe, for speaking about the JCO article, “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.” Join us again for the latest JCO simultaneous publications. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of World Lung Conference. 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.  

In this special WCLC 2025 episode of Lung Cancer Considered, hosts Dr. Narjust Florez and Dr. Stephen Liu discuss daily highlights from the conference. Dr. Tina Cascone discusses results from the NADIM ADJUVANT Phase III trial. Dr. Jacie Jiaqi Law shares survival outcomes of VATS compared to open lobectomy, and Dr. Corinne Faivre-Finn and Dr. Shankar Siva summarize results from the EA5181 trial of concurrent and consolidation durvalumab after chemoradiation for unresectable NSCLC and hypofractionation vs conventional fractionation for LS SCLC.

Are you aware of the latest developments for treating EGFR mutation–positive advanced/metastatic NSCLC? Credit available for this activity expires: 8/29/2026 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/1002869?ecd=bdc_podcast_libsyn_mscpedu

Send us a textWhat if AI could predict cancer outcomes better than traditional methods—and at a fraction of the cost? In this episode, I explore how multimodal AI is reshaping lung and prostate cancer predictions and why integration challenges still stand in the way.Episode Highlights with Timestamps:[00:02:57] Agentic AI in toxicologic pathology – what it is and how it could orchestrate workflows.[00:05:40] Grandium desktop scanners – making histology studies more accessible and efficient.[00:08:03] Clover framework – a cost-effective multimodal model combining vision + language for pathology.[00:13:40] NSCLC study (Beijing Chest Hospital) – AI predicts progression-free and overall survival with high accuracy.[00:17:58] Prostate cancer prognostic model (Cleveland Clinic & US partners) – validating AI-enabled Pathomic PRA test.[00:23:35] Thyroid neoplasm classification – challenges for AI in distinguishing overlapping histopathological features.[00:34:49] Real-world Belgium case study – AI integration into prostate biopsy workflow reduced IHC testing and turnaround time.[00:41:03] Lessons learned – adoption hurdles, system integration, and why change management is essential for successful digital transformation.Resources from this EpisodeWorld Tumor Registry – A global open-access repository for histopathology images: World Tumor RegistryBeijing Chest Hospital NSCLC AI Prognostic Study – Prognosis prediction using multimodal models.Cleveland Clinic Pathomic PRA Study – Independent validation of AI-enabled prostate cancer risk assessment.Grandium Scanners – Compact desktop scanners for histology slides: Grandium.aiSupport the showBecome a Digital Pathology Trailblazer get the "Digital Pathology 101" FREE E-book and join us!

In today's episode, supported by Nuvation Bio, we spoke with Joel Neal, MD, PhD, and Christian Rolfo, MD, PhD, about the FDA approval of taletrectinib (Ibtrozi) for the treatment of patients with locally advanced or metastatic, ROS1-positive non–small cell lung cancer (NSCLC). Dr Neal is a professor of medicine in the Division of Oncology at the Stanford Cancer Institute at Stanford University in Palo Alto, California. Dr Rolfo is the director of the Division of Medical Oncology at The Ohio State University Comprehensive Cancer Center—James and a professor in the College of Medicine at The Ohio State University in Columbus. In our conversation, Drs Neal and Rolfo discussed the significance of this approval, key data from the pivotal phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials, and taletrectinib's current role in the NSCLC treatment paradigm.

In today's episode, supported by Boehringer Ingelheim, we spoke with Ticiana Leal, MD, and Misako Nagasaka, MD, PhD, about the FDA approval of zongertinib (Hernexeos) for previously treated patients with HER2 TKD–mutant advanced non–small cell lung cancer (NSCLC). Dr Leal is an associate professor and director of the Thoracic Medical Oncology Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta, Georgia; as well as medical director of the Clinical Trials Office and leader of the Lung Cancer Disease Team at the Winship Cancer Institute of Emory University. Dr Nagasaka is an associate professor of medicine in the Division of Hematology and Oncology at the University of California, Irvine (UCI) School of Medicine; as well as a medical oncologist at UCI Health. In our conversation, Drs Leal and Nagasaka discussed the significance of this approval, key efficacy and safety findings from the pivotal phase 1 Beamion LUNG-1 trial (NCT04886804), and where zongertinib currently fits into the NSCLC treatment paradigm.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. While the development of targeted therapies has improved outcomes for many patients with EGFR-mutated NSCLC, those with rare EGFR variants often face limited treatment options, especially when the disease involves the central nervous system (CNS). A recent research paper, titled “Durable complete response in leptomeningeal disease of EGFR mutated non-small cell lung cancer to amivantamab, an EGFR-MET receptor bispecific antibody, after progressing on osimertinib” published in Volume 16 of Oncotarget, describes a patient with NSCLC harboring two uncommon EGFR mutations—G719A and A289V—who experienced a prolonged and clinically significant response to amivantamab monotherapy, after prior treatments had failed. Full blog - https://www.oncotarget.org/2025/08/26/amivantamab-monotherapy-in-rare-egfr-mutated-advanced-nsclc/ Paper DOI - https://doi.org/10.18632/oncotarget.28730 Correspondence to - Young Kwang Chae - young.chae@northwestern.edu Video short - https://www.youtube.com/watch?v=UEiCz834a8c Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28730 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, amivantamab, monotherapy, rare EGFR mutation, NSCLC, leptomeningeal disease About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Welcome back to the Oncology Brothers podcast! In this episode, Drs. Rohit & Rahul Gosain are joined by Dr. Joshua Sabari from the NYU Langone Cancer Center to discuss the exciting recent approval of Zongertinib, the first oral TKI for HER2-positive lung cancer. We dived deep into the prevalence of HER2 mutations in non-small cell lung cancer, the study design and findings from the Beamion LUNG-1 trial, and the implications of this new therapy in clinical practice. Dr. Sabari shared insights on the efficacy of Zongertinib, including impressive response rates and progression-free survival data, as well as its side effect profile compared to other treatments like trastuzumab deruxtecan (T-DXd). Key topics covered in this episode: •⁠  ⁠Overview of HER2 mutations in lung cancer •⁠  ⁠Study design and results of the Beamion LUNG-1 •⁠  ⁠Comparison of Zongertinib and T-DXd in treatment settings •⁠  ⁠Management of common side effects associated with Zongertinib •⁠  ⁠Future directions for HER2-targeted therapies Join us for this informative discussion as we explore the latest advancements in lung cancer treatment and what they mean for patients and clinicians alike. Don't forget to subscribe for more episodes on new approvals, side effect management, and practice-changing data in oncology! Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/

In this podcast, experts Erminia Massarelli, MD, PhD, MS; Jorge J. Nieva, MD; Sandip Patel, MD; and Ignacio I. Wistuba, MD, discuss new therapies for patients with c-Met–overexpressing non–small cell lung cancer.

LCC in Greek: Virtual Tumor Board - ALK NSCLC by IASLC

In today's episode, supported by Daiichi-Sankyo, we spoke with Ronan J. Kelly, MD, MBA, FASCO; and Michelle Shiller, DO, AP/CP, MGP, about HER2 immunohistochemistry (IHC) testing in non–small cell lung cancer (NSCLC). Kelly is director of the Charles A. Sammons Cancer Center and chief science officer at Baylor University Medical Center in Dallas, Texas; the W.W. Caruth Jr. Endowed Chair of Immunology at Baylor University Medical Center; chief of Oncology at Baylor Scott & White Health System; founder and medical director of the Texas Cancer Interception Institute; a clinical professor at the Texas A&M University College of Medicine; an adjunct associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland; and a professor in the Clinical Sciences Division at the Translational Genomics Research Institute in Phoenix, Arizona. Shiller is a molecular genetic pathologist at Baylor University Medical Center.  In our conversation, Drs Kelly and Shiller discussed the importance of performing IHC testing for HER2 in NSCLC, how IHC results may influence treatment decision-making beyond the scope of next-generation sequencing results, and recommendations for more efficient and collaborative IHC testing implementation in clinical practice. 

In this episode of the Oncology Brothers podcast, Drs. Rohit & Rahul Gosain welcome Dr. Jacob Sands, a thoracic medical oncologist from the Dana-Farber Cancer Institute, to discuss the recent FDA approval of Dato-DXD (datopotamab deruxtecan) for previously treated EGFR-mutated non-small cell lung cancer (NSCLC). Key Topics: •⁠  ⁠Overview of Dato-DXd and its FDA approval •⁠  ⁠Mechanism of action and study design of the TROPION Lung trials •⁠  ⁠Efficacy and safety profile of Dato-DXd •⁠  ⁠Management of side effects and clinical pearls •⁠  ⁠Treatment sequencing for EGFR-mutated NSCLC Join us as we dive into the details of the TROPION Lung trials that led to this significant approval, the mechanism of action of Dato-DXd, and the implications for patients with various EGFR mutations.  Dr. Sands shared insights on the study design, efficacy, and tolerability of this new antibody-drug conjugate, as well as important clinical pearls for managing side effects such as stomatitis, dry eyes, and interstitial lung disease (ILD). We also explored the current treatment landscape for EGFR-mutated NSCLC, including the sequencing of therapies and the potential role of Dato-DXd in clinical practice. Tune in for an informative discussion that highlights the exciting advancements in oncology and the hope they bring to patients. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and check out our other episodes for more insights into the world of oncology!

A new ERBB2 (HER2) targeting TKI is approved for NSCLC. We review the characteristics of the drug and summarize the current landscape in treating HER-mutated advanced NSCLC.

FDA Approval: Zongertinib for HER2 Mutant NSCLC by IASLC

In this episode, listen to Kelly Romo, PharmD, BCOP; and Shauna Kraft, PharmD, BCOP, share their takeaways from a live webinar on available emerging subcutaneous immunotherapy options for patients with cancer including:Basic mechanism of action and role of hyaluronidase in subcutaneous immunotherapy formulation and available dosing/schedulesAvailable pharmacodynamics/pharmacokinetics, efficacy, and safety data for subcutaneous immunotherapy formulationsCurrent and potential models for administration of subcutaneous immunotherapy in the inpatient setting and day-to-day considerationsPresenters:Kelly Romo, PharmD, BCOPManager, Oncology Medical Drug Management and Customer InitiativesBlue Cross Blue Shield MichiganDetroit, MichiganShawna Kraft, PharmD, BCOPClinical Pharmacist, SpecialistMichigan Medicine, Rogel Cancer CenterClinical Associate ProfessorUniversity of Michigan College of PharmacyAnn Arbor, MichiganResources:Consolidate your learning with a recording from an on-demand webcast, download the slides associated with this discussion, or read an expert text module or commentary on this topic. 

In this episode, listen to Kelly Romo, PharmD, BCOP; and Shauna Kraft, PharmD, BCOP, share their takeaways from a live webinar on available emerging subcutaneous immunotherapy options for patients with cancer including:Basic mechanism of action and role of hyaluronidase in subcutaneous immunotherapy formulation and available dosing/schedulesAvailable pharmacodynamics/pharmacokinetics, efficacy, and safety data for subcutaneous immunotherapy formulationsCurrent and potential models for administration of subcutaneous immunotherapy in the inpatient setting and day-to-day considerationsPresenters:Kelly Romo, PharmD, BCOPManager, Oncology Medical Drug Management and Customer InitiativesBlue Cross Blue Shield MichiganDetroit, MichiganShawna Kraft, PharmD, BCOPClinical Pharmacist, SpecialistMichigan Medicine, Rogel Cancer CenterClinical Associate ProfessorUniversity of Michigan College of PharmacyAnn Arbor, MichiganResources:Consolidate your learning with a recording from an on-demand webcast, download the slides associated with this discussion, or read an expert text module or commentary on this topic. 

Lung cancer, particularly non-small cell lung cancer (NSCLC), is the deadliest cancer worldwide. Cigarette smoking is one of the main causes, but not every smoker develops the disease. This suggests that other biological factors help determine who develops cancer. Researchers from the Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis, and from the Richard L. Roudebush Veterans Affairs Medical Center have now found that cigarette smoke, combined with a weakened DNA repair system, can trigger the early stages of lung cancer, particularly NSCLC. This work, led by first author Nawar Al Nasralla and corresponding author Catherine R. Sears, was recently published in Volume 16 of Oncotarget. Full blog - https://www.oncotarget.org/2025/08/11/cigarette-smoke-and-weak-dna-repair-a-double-hit-behind-lung-cancer-risk/ Paper DOI - https://doi.org/10.18632/oncotarget.28724 Correspondence to - Catherine R. Sears - crufatto@iu.edu Video short - https://www.youtube.com/watch?v=UEiCz834a8c Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28724 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, DNA repair, DNA damage, lung adenocarcinoma, squamous cell carcinoma, Xeroderma Pigmentosum Group C (XPC) To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

i3 Health recently launched an exciting new online educational activity, “What's New with HER2: Charting New Paths in NSCLC Care.” This two-part series dives deep into the evolving role of HER2 in non–small cell lung cancer (NSCLC). In a special interview, Dr. Julia Kathleen Rotow—Clinical Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School—shares the latest breakthroughs in treating HER2-mutated NSCLC. She highlights why ongoing medical education is crucial in this fast-changing field and offers her insights on where HER2-targeted therapies are headed next. Stay tuned after the interview to listen to Module 1 of this accredited activity! Click below to complete the claim your CE credit: Module 1: https://bit.ly/49NCaQu Click below to complete the next Module in this series, Current and Emerging Treatments for HER2-Mutated NSCLC Module 2: https://bit.ly/405xEJO

i3 Health recently launched an exciting new online educational activity, “What's New with HER2: Charting New Paths in NSCLC Care.” This two-part series dives deep into the evolving role of HER2 in non–small cell lung cancer (NSCLC). In a special interview, Dr. Julia Kathleen Rotow—Clinical Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School—shares the latest breakthroughs in treating HER2-mutated NSCLC. She highlights why ongoing medical education is crucial in this fast-changing field and offers her insights on where HER2-targeted therapies are headed next. Stay tuned after the interview to listen to Module 1 of this accredited activity! Click below to complete the claim your CE credit: Module 2: https://bit.ly/405xEJO Click below to complete the Module 1 from this series, HER2 in NSCLC: Actionable Insights and Testing Recommendations Module 1: https://bit.ly/49NCaQu

In today's episode, we had the pleasure of speaking with Martin F. Dietrich, MD, PhD, about updates and best practices for HER2 and MET immunohistochemistry (IHC) testing for patients with non–small cell lung cancer (NSCLC). Dr Dietrich is a medical oncologist at Cancer Care Centers of Brevard in Rockledge, Florida; as well as an assistant professor of internal medicine at the University of Central Florida in Orlando.  In our exclusive interview, Dr Dietrich discussed the rationale for testing for these mutations in patients with NSCLC, standard practices for implementing these tests in the clinic, and when testing may be appropriate at disease progression. 

In a discussion with CancerNetwork®, Jacob Sands, MD, assistant professor of Medicine at Harvard Medical School, thoracic oncologist at the Dana-Farber Cancer Institute, and investigator of the phase 2 TROPION-Lung05 trial (NCT04484142) and phase 3 TROPION-Lung01 trial (NCT04656652), which supported the accelerated approval of datopotamab deruxtecan-dlnk (dato-DXd; Datroway) in pretreated EGFR-mutant metastatic NSCLC in June 2025, discussed safety and efficacy considerations for the agent's use.1-3 He began by outlining a combined cohort of the TROPION-Lung05 and TROPION-Lung01 trials, which collectively showed an efficacy benefit with dato-DXd in patients with EGFR-mutant disease vs docetaxel. In the combined cohort, the median progression-free survival with dato-DXd reached 5.8 months, and the median overall survival was 15.6 months. Additional efficacy data revealed an objective response rate of 45% (95% CI, 35%-54%) and a median duration of response of 6.5 months (95% CI, 4.2-8.4).  Furthermore, Sands highlighted the most common toxicities observed with dato-DXd in this population, which included stomatitis, interstitial lung disease (ILD), and ocular toxicities. He also reviewed management strategies to mitigate their incidence and severity. Specifically, remedies include prophylaxis, oral hygiene, and dose reductions for stomatitis; using preservative-free eye drops and ophthalmology visits for ocular toxicity management and prevention; and monitoring for any incidence of high-grade ILD. He then touched upon next steps for research in this disease state, including the phase 2 ORCHARD trial (NCT03944772) evaluating dato-DXd with osimertinib (Tagrisso) in the second-line setting after progression on osimertinib and the phase 3 TROPION-Lung15 trial (NCT06417814), which is evaluating chemotherapy vs dato-DXd alone or with osimertinib.4,5 Sands concluded by discussing the implications for toxicity management in patients who experience responses that exceed median outcomes, suggesting that the toxicity profile may be more severe for this group. Emphasizing the broadness of outcomes with any drug, he expressed that patients with experiences that deviate from the observed median outcome are an important consideration for clinical practice. References Sands J, Ahn MJ, Lisberg A, et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. J Clin Oncol. Published online January 6, 2025. doi:10.1200/JCO-24-01349 Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III TROPION-Lung01 study. J Clin Oncol. Published online September 9, 2024. doi:10.1200/JCO-24-01544  FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. News release. FDA. June 23, 2025. Accessed July 29, 2025. https://tinyurl.com/mtay7ab9 Yu HA, Goldberg SB, Le X, et al. Biomarker-directed phase II platform study in patients with EGFR sensitizing mutation-positive advanced/metastatic non-small cell lung cancer whose disease has progressed on first-line osimertinib therapy (ORCHARD). Clin Lung Cancer. 2021;22(6):601-606. doi:10.1016/j.cllc.2021.06.006 A study to investigate the efficacy and safety of dato-DXd with or without osimertinib compared with platinum based doublet chemotherapy in participants with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (TROPION-Lung15). ClinicalTrials.gov. Updated July 16, 2025. Accessed July 29, 2025. https://tinyurl.com/56z3dmsp

Kevin Chen, PharmD, MS, BCOP, CPP, and Amanda Cass, PharmD, BCPS, BCOP, share key insights about ROS1, non-small cell lung cancer, and the new approved drug taletrectinib.

In today's episode, we spoke with Joshua K. Sabari, MD, about the use of telisotuzumab vedotin-tllv (Emrelis) in patients with c-MET–overexpressing, nonsquamous, EGFR wild-type advanced non–small cell lung cancer (NSCLC). Dr Sabari is an assistant professor in the Department of Medicine at the New York University Grossman School of Medicine; as well as the director of High Reliability Organization Initiatives at the Perlmutter Cancer Center in New York.  In our exclusive interview, Dr Sabari highlighted key data from the phase 2 LUMINOSITY study (NCT03539536) investigating telisotuzumab vedotin in this patient population, the significance of targeting c-Met overexpression, and how findings from the ongoing phase 2 TeliMET NSCLC-04 trial (NCT06568939) of telisotuzumab vedotin in patients with c-Met–overexpressing, locally advanced or metastatic nonsquamous NSCLC may further influence the NSCLC treatment paradigm. 

FDA Approval: Datopotamab Deruxtecan for EGFR NSCLC by IASLC

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

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

Prof Marina Garassino, Dr John Heymach, Prof Solange Peters and moderator Dr Jacob Sands present key data from the ASCO 2025 Annual Meeting on the management of metastatic NSCLC without targetable mutations, as well as emerging evidence on the role of antibody-drug conjugates for patients with select actionable genomic alterations. CME information and select publications here.

Check out this week's QuadCast as we highlight a PSMA Theranostic contender, new guidelines (and name) for GBM, current management limitations in NSCLC, and more. Check out the website and subscribe to the newsletter! www.quadshotnews.com Founders & Lead Authors: Laura Dover & Caleb Dulaney Podcast Host: Sam Marcrom

LCC in Portuguese: Virtual Tumor Board - EGFR NSCLC by IASLC

In this episode of the Oncology Brothers podcast, Drs. Rahul and Rohit Gosain are joined by Dr. Deepa Rangachari, a thoracic medical oncologist and fellowship program director at Beth Israel Deaconess Medical Center. Together, they dived deep into the treatment algorithms for early-stage non-small cell lung cancer (NSCLC) with a focus on curative intent. Key topics discussed include: •⁠  ⁠The importance of staging and lymph node evaluation in treatment planning. •⁠  ⁠The role of neoadjuvant chemoimmunotherapy and the impact of recent trial data, including the CHECKMATE 816 trial. •⁠  ⁠The significance of actionable mutations and the use of targeted therapies like Osimertinib and Alectinib. •⁠  ⁠The evolving role of ctDNA in treatment decisions and monitoring. •⁠  ⁠Insights into the management of side effects associated with Osimertinib and Alectinib. •⁠  ⁠The standard of care for unresectable stage 3 NSCLC, including concurrent chemoradiation and the use of Durvalumab. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Join us for an informative discussion that highlights the latest advancements in lung cancer treatment and the importance of personalized care. Don't forget to check out our other episodes in the lung cancer treatment algorithm series!

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 information, and to apply for credit, please visit us at PeerView.com/ZEV865. CME/MOC/AAPA credit will be available until June 30, 2026.Precision Matters in NSCLC: Everything You Need to Know About Biomarker Testing and Targeted Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and LUNGevity Foundation, ONC Brothers. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AbbVie, AstraZeneca, Johnson & Johnson, Lilly, Nuvalent, Nuvation Bio, and Rigel 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 information, and to apply for credit, please visit us at PeerView.com/ZEV865. CME/MOC/AAPA credit will be available until June 30, 2026.Precision Matters in NSCLC: Everything You Need to Know About Biomarker Testing and Targeted Therapies In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and LUNGevity Foundation, ONC Brothers. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by independent educational grants from AbbVie, AstraZeneca, Johnson & Johnson, Lilly, Nuvalent, Nuvation Bio, and Rigel Pharmaceuticals, Inc.Disclosure information is available at the beginning of the video presentation.

Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Ross Camidge, a leading thoracic medical oncologist from the University of Colorado, to discuss the recent approval of telisotuzumab-vedotin (Teliso-V) for metastatic non-small cell lung cancer (NSCLC) with C-met overexpression, based on the LUMINOSITY trial. Join us as we explore: • The mechanism of action of telisotuzumab and its role as an antibody-drug conjugate. • The prevalence of C-met overexpression in NSCLC and its implications for testing and treatment. • Key findings from the Luminosity trial, including response rates and study design. • The importance of C-met testing in clinical practice. • Management of side effects associated with telisotuzumab, particularly peripheral neuropathy. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ This episode is packed with valuable insights for oncologists and healthcare professionals navigating the evolving landscape of lung cancer treatment. Don't miss out on this informative discussion!

In today's episode, supported by Daiichi Sankyo, we had the pleasure of speaking with Misako Nagasaka, MD, PhD, about the use of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in pretreated patients with HER2-mutated non–small cell lung cancer (NSCLC). Dr Nagasaka is an associate professor in the Division of Hematology and Oncology and the Division of Medicine at the University of California Irvine School of Medicine. In our exclusive interview, Dr Nagasaka discussed current second-line treatment standards for patients with HER2-mutated NSCLC, how the use of T-DXd in this setting may evolve with the emergence of investigational agents, and the importance of integrating HER2 immunohistochemistry testing into clinical practice.