Podcasts about nsclc

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.

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. 

Host: Gerard A. Silvestri MD, MS, Master FCCP Guest: Fabien Maldonado, MD, FCCP Guest: Adam H. Fox, MD, MSc Cutting-edge biopsy methods and streamlined biomarker testing are transforming early-stage non-small cell lung cancer (NSCLC) care. Hear from Drs. Gerard Silvestri, Fabien Maldonado, and Adam Fox as they discuss the evolution of bronchoscopic techniques, insights from landmark trials, and the role of pragmatic clinical research in refining biopsy approaches. Dr. Silvestri is a pulmonologist and the Hillenbrand Professor of Thoracic Oncology at the Medical University of South Carolina; Dr. Maldonado is a Professor of Medicine and Thoracic Surgery, the Pierre Massion Director in Lung Cancer Research, and the Director of Interventional Pulmonology Research at Vanderbilt University; and Dr. Fox is a pulmonologist and Assistant Professor of Medicine at the Medical University of South Carolina. This program is produced in partnership with the American College of Chest Physicians and is sponsored by AstraZeneca.

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 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

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

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

Following the FDA approval of taletrectinib (Ibtrozi) for patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC), CancerNetwork® spoke with Jorge Nieva, MD, about how this regulatory decision may impact the treatment paradigm for this disease. The approval was supported by findings from the phase 2 TRUST-I trial (NCT04395677) and the phase 2 TRUST-II trial (NCT04919811). The total efficacy population included 157 patients who had no prior treatment with a ROS1 tyrosine kinase inhibitor (TKI) and 113 who were previously treated with a ROS1 TKI. Topline results showed an objective response rate (ORR) of 90% (95% CI, 83%-95%) in TRUST-I and 85% (95% CI, 73%-93%) in TRUST-II among patients who had no prior treatment. Of those with pretreated disease, the respective ORRs were 52% (95% CI, 39%-64%) and 62% (95% CI, 46%-75%) in each study population. According to Nieva, an associate professor of clinical medicine at the Keck School of Medicine of the University of Southern California, taletrectinib may offer advantages over other therapies in the ROS1-positive metastatic NSCLC space based on its improved central nervous system (CNS) toxicity profile and “excellent” response and progression-free survival data. He stated that taletrectinib would become the go-to first-line agent in his practice. Additionally, he discussed strategies for mitigating toxicities related to taletrectinib such as nausea and diarrhea, and highlighted the need for additional research to improve immunotherapy options in NSCLC.  “I'm very happy that we have choices for patients, and I'm very happy that we have such a wide variety of drugs, but we still need to do better, and we need to find better ways of using these agents because they're still not cures for the majority of patients,” Nieva stated. “While these drugs can be helpful at debulking tumors, we still need to do a lot more work [to do] on making this a disease of the past for those patients who have it.” Reference FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. News release. FDA. June 11, 2025. Accessed July 8, 2025. https://tinyurl.com/yc4f379m

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.

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.

In this episode of Lung Cancer Considered, host Dr. Stephen Liu moderates a Virtual Tumor Board case with Dr. Chunxia Su and Dr. Collin Blakely. The case explores resectable EGFR NSCLC.

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/AWM865. CME/MOC/AAPA credit will be available until June 30, 2026.Strategies for Immunotherapy Success in NSCLC: How to Incorporate Modern ICI Platforms Across the Disease Continuum In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and LUNGevity Foundation. 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 through independent educational grants from Bristol Myers Squibb, Merck & Co., Inc., Rahway, NJ, USA, and Regeneron 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!

BUFFALO, NY – June 27, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Molecular landscape of HER2-mutated non-small cell lung cancer in Northeastern Brazil: Clinical, histopathological, and genomic insights.” In this study, researchers led by first authors Cleto Dantas Nogueira from the Federal University of Ceará and Argos Pathology Laboratory and Samuel Frota from Argos Pathology Laboratory, along with corresponding author Fabio Tavora from the previously mentioned institutions and Messejana Heart and Lung Hospital, investigated how HER2 gene mutations appear in cases of non-small cell lung cancer (NSCLC) in Northeastern Brazil. The team found that HER2 mutations showed significant genetic diversity and were often associated with other cancer-related genetic changes. These findings revealed diagnostic and treatment challenges in a population that is rarely studied, emphasizing the need for expanded access to molecular testing and targeted therapies. HER2 mutations are a known factor in several cancers, including breast and gastric cancers. In lung cancer—particularly NSCLC—these mutations are less common but remain clinically significant. Most existing research on HER2-mutated lung cancer focuses on high-income countries, leaving important gaps in knowledge about underrepresented regions such as Latin America. This study helps fill that gap by analyzing 13 patients with HER2-mutated NSCLC using clinical, pathological, and genomic data. The patients ranged in age from 34 to 82 years, and more than half were women. About half had never smoked. Their tumors often displayed complex genetic profiles, including additional mutations in genes such as TP53, KRAS, and STK11. The most common HER2 mutation identified was an insertion in exon 20, a known hotspot for activating mutations. “Trastuzumab deruxtecan (T-DXd) is the first HER2-targeted agent to show clinical efficacy in HER2-mutant non-small cell lung cancer (HER2m NSCLC).” Treatment strategies among the patients varied. Only one individual received HER2-targeted therapy. Most were treated with surgery, chemotherapy, immunotherapy, or a combination of these approaches. Outcomes also differed, with some patients surviving for years and others dying within months of diagnosis. These findings reinforce the need for early diagnosis and improved access to advanced treatments, particularly in low-resource settings. The study emphasizes the value of comprehensive molecular profiling in NSCLC. Because HER2 mutations often occur alongside other genetic alterations, full genomic analysis is crucial for guiding treatment decisions. Yet, such testing is not always available. The researchers propose a tiered diagnostic approach, beginning with basic screening and expanding to more advanced tests when necessary, to enhance patient care. This study provides valuable insights into the molecular characteristics of HER2-mutated NSCLC in a Brazilian population, highlighting the complexity and clinical relevance of these alterations. Larger studies are needed to clarify the prevalence and prognostic significance of HER2 mutations, as well as their impact on treatment response and survival. This knowledge is essential for advancing effective HER2-targeted therapies. The findings also support broader implementation of international clinical guidelines in Latin America and highlight the critical need to include underrepresented populations in cancer research. DOI - https://doi.org/10.18632/oncotarget.28737 Correspondence to - Fabio Tavora - stellacpak@outlook.com Video short - https://www.youtube.com/watch?v=hr5R9iDBFFI To learn more about Oncotarget, please visit https://www.oncotarget.com. MEDIA@IMPACTJOURNALS.COM

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.

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, subscribe wherever you get your podcast. 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. More on today's speakers:    Dr. Vamsi Velcheti   @VamsiVelcheti    Dr. Nathan Pennell   @n8pennell   Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn   ASCO on BlueSky   Disclosures:   Dr. Vamsi Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   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   Dr. Nathan Pennell:     Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron    Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

In this episode of Lung Cancer Considered, host Dr. Stephen Liu discusses the recent FDA approval of taletrectinib, a next-generation ROS1 kinase inhibitor, for NSCLC with a ROS1 gene fusion. Dr. Enriqueta Felip and Dr. Jorge Nieva join the conversation to help review the data and offer help place this new agent in the proper perspective.

Please visit answersincme.com/ZDE860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in lung cancer discusses best practices for implementing biomarker testing in non-small cell lung cancer (NSCLC) management. Upon completion of this activity, participants should be better able to: Apply current guideline recommendations for biomarker testing to the management of patients with NSCLC, Outline practical strategies within the multidisciplinary team to optimize biomarker testing for patients with NSCLC; and Discuss methods to link biomarker testing to treatment decision-making for patients with NSCLC.

Antibody drug conjugates, or ADCs, are still holding on to their spot as one of the hottest areas in cancer care—and AbbVie, like many of its peers, has embraced the trend head-on. In this week’s episode of "The Top Line," Fierce Pharma’s Zoey Becker speaks with Daejin Abidoye, M.D., AbbVie’s vice president and therapeutic area head for solid tumor oncology. They discuss the company’s evolution, trends from this year’s American Society of Clinical Oncology meeting and what’s ahead for ADCs in oncology. AbbVie, a newer player in the ADC space, recently earned FDA approval for Emrelis in adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have previously received systemic therapy. With a robust pipeline of ADCs in development, Abidoye envisions a bright future for the class—one that could herald “a new era” of cancer treatment beyond traditional chemotherapy. To learn more about the topics in this episode: AbbVie advances solid tumor agenda with FDA nod for lung cancer ADC Emrelis AbbVie pays $10B to acquire ImmunoGen, doubling down on red-hot ADC cancer field Replacing chemotherapy with ADCs? AbbVie rebuilds next-gen assets after Rova-T flop See omnystudio.com/listener for privacy information.

In today's episode, we spoke with Jonathan W. Goldman, MD, about the phase 2 LUMINOSITY study (NCT03539536) evaluating telisotuzumab vedotin-tllv (Teliso-V; Emrelis) in patients with c-MET protein–overexpressing, nonsquamous, EGFR wild-type advanced non–small cell lung cancer (NSCLC). Dr Goldman is a professor of medicine in the Division of Hematology/Oncology at UCLA, as well as director of Clinical Trials in Thoracic Oncology, associate director of Early Drug Development, and chair of the University of California Lung Cancer Consortium.