Podcasts about her2

With the increasing incidence of colorectal cancer in those less than 50 years of age, one must wonder how many patients present with a Stage IV diagnosis. Take a deep dive with us discussing the management of metastatic colorectal cancer by joining our team and guests, Drs. Cathy Eng, Michael D'Angelica, and Nina Sanford.Hosts: - Dr. Janet Alvarez - General Surgery Resident at New York Medical College/Metropolitan Hospital Center- Dr. Wini Zambare – General Surgery Resident at Weill Cornell Medical Center/New York Presbyterian- Dr. Philip Bauer, Assistant Professor of Surgery, Division of Colon and Rectal Surgery, The Ohio State University Wexner Medical Center, Arthur G. James Cancer Hospital-  Dr. J. Joshua Smith MD, PhD, Chair, Department of Colon and Rectal Surgery at MD Anderson Cancer Center Guest Speakers:- Dr. Michael D'Angelica MD, FACS – Hepatopancreatobiliary Surgery, Memorial Sloan Kettering Cancer Center, Enid A. Haupt Chair in Surgery, Vice Chair, Education- Dr. Cathy Eng MD, FACP - Division of Hematology and Oncology, Vanderbilt-Ingram Cancer Center, David H. Johnson Endowed Chair in Surgical and Medical Oncology, Professor of Medicine, Hematology and Oncology, VICC Associate Director for Strategic Relations and Research Partnerships, Executive Director, Young Adult Cancers Program - Dr. Nina Sanford, MD – Radiation Oncology, UT Southwestern Medical Center, Chief of Gastrointestinal Radiation Oncology Service, Associate Professor Learning Objectives:1.     Review the epidemiology, prognosis, and common metastatic patterns of metastatic colorectal cancer (mCRC).2.     Discuss the role of systemic chemotherapy and targeted therapies in the first- and subsequent-line treatment of mCRC, including the impact of molecular biomarkers such as MSI/MMR, RAS, BRAF, and HER2.3.     Evaluate the indications and timing of surgical and locoregional therapies for metastatic colorectal cancer, particularly in patients with liver-limited or oligometastatic disease.4.     Describe the multidisciplinary management of mCRC, including the roles of radiation therapy, systemic therapy sequencing, and palliative interventions to optimize outcomes and quality of life.References:Singh, M., Morris, V. K., Bandey, I. N., Hong, D. S. & Kopetz, S. Advancements in combining targeted therapy and immunotherapy for colorectal cancer. Trends Cancer 10, 598–609 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/38821852/Napolitano, S. et al. BRAFV600E mutant metastatic colorectal cancer: Current advances in personalized treatment and future perspectives. Cancer Treat. Rev. 134, (2025). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/40009904/Ciardiello, F. et al. Clinical management of metastatic colorectal cancer in the era of precision medicine. CA. Cancer J. Clin. 72, 372–401 (2022). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/35472088/Kim, S. Y. & Kim, T. W. Current challenges in the implementation of precision oncology for the management of metastatic colorectal cancer. ESMO Open 5, e000634 (2020). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/32188714/Biller, L. H. & Schrag, D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA 325, 669–685 (2021). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/33591350/Smith, J. J. et al. Genomic stratification beyond Ras/B-Raf in colorectal liver metastasis patients treated with hepatic arterial infusion. Cancer Med. 8, 6538–6548 (2019). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/31503397/Saadat, L. V. et al. Hepatic Artery Infusion Chemotherapy Compared to Transarterial Radioembolization For Unresectable Colorectal Liver Metastases. Ann. Surg. 10.1097/SLA.0000000000006851 doi:10.1097/SLA.0000000000006851. PubMed Link: https://pubmed.ncbi.nlm.nih.gov/?term=10.1097/SLA.0000000000006851 (Linked via DOI search as the direct PMID is still indexing)Xiao, A. & Fakih, M. KRAS G12C Inhibitors in the Treatment of Metastatic Colorectal Cancer. Clin. Colorectal Cancer 23, 199–206 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/38825433/André, T. et al. Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer. N. Engl. J. Med. 383, 2207–2218 (2020). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/33264544/Morris, V. K. et al. Treatment of Metastatic Colorectal Cancer: ASCO Guideline. J. Clin. Oncol. 41, 678–700 (2023). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/36252154/Xu, Z. et al. Treatments for Stage IV Colon Cancer and Overall Survival. J. Surg. Res. 242, 47–54 (2019). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/31071604/Smith, J. J. & D'Angelica, M. I. Surgical Management of Hepatic Metastases of Colorectal Cancer. Hematol. Oncol. Clin. North Am. 29, 61–84 (2015). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/25475573/Strickler, J. H. et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 24, 496–508 (2023). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/37142372/Kruijssen, D. E. W. van der et al. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group. Ann. Oncol. 35, 769–779 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/38852675/Hitchcock, K. E., Romesser, P. B. & Miller, E. D. Local Therapies in Advanced Colorectal Cancer. Hematol. Oncol. Clin. North Am. 36, 553–567 (2022). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/35562258/Hitchcock, K. E. et al. Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur). BMC Cancer 24, 201 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/38350888/Adam, R. et al. Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial. The Lancet 404, 1107–1118 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/39306468/Elez, E. et al. Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer. N. Engl. J. Med. 392, 2425–2437 (2025). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/40444708/***Fellowship Application Link: https://forms.gle/QSUrR2GWHDZ1MmWC6Please visit https://behindtheknife.org to access other high-yield surgical education podcasts, videos and more.  If you liked this episode, check out our recent episodes here: https://behindtheknife.org/listenBehind the Knife Premium:General Surgery Oral Board Review Course: https://behindtheknife.org/premium/general-surgery-oral-board-reviewTrauma Surgery Video Atlas: https://behindtheknife.org/premium/trauma-surgery-video-atlasDominate Surgery: A High-Yield Guide to Your Surgery Clerkship: https://behindtheknife.org/premium/dominate-surgery-a-high-yield-guide-to-your-surgery-clerkshipDominate Surgery for APPs: A High-Yield Guide to Your Surgery Rotation: https://behindtheknife.org/premium/dominate-surgery-for-apps-a-high-yield-guide-to-your-surgery-rotationVascular Surgery Oral Board Review Course: https://behindtheknife.org/premium/vascular-surgery-oral-board-audio-reviewColorectal Surgery Oral Board Review Course: https://behindtheknife.org/premium/colorectal-surgery-oral-board-audio-reviewSurgical Oncology Oral Board Review Course: https://behindtheknife.org/premium/surgical-oncology-oral-board-audio-reviewCardiothoracic Oral Board Review Course: https://behindtheknife.org/premium/cardiothoracic-surgery-oral-board-audio-reviewDownload our App:Apple App Store: https://apps.apple.com/us/app/behind-the-knife/id1672420049Android/Google Play: https://play.google.com/store/apps/details?id=com.btk.app&hl=en_US

Featuring perspectives from Dr Haley Ellis, Prof Eric Van Cutsem and Dr Zev Wainberg, moderated by Dr Lionel A Kankeu Fonkoua, including the following topics: Biliary tract cancer progressing on first-line therapy (0:00) Gallbladder cancer (5:01) Biliary tract cancer with multiple biomarker targets (8:52) CME information and select publications

Dr Haley Ellis from Mass General Brigham Cancer Institute in Boston, Massachusetts, Prof Eric Van Cutsem from University Hospitals Leuven in Belgium, Dr Zev Wainberg from UCLA Jonsson Comprehensive Cancer Center in Los Angeles, California, and moderator Dr Lionel A Kankeu Fonkoua from Mayo Clinic in Rochester, Minnesota, discuss recent data and provide their perspectives on the management of HER2-positive GI cancers.CME information and select publications here.

In this episode of the Better Than Before Breast Cancer podcast, Laura Lummer sits down with Chelsea Hassink to talk about her experience navigating a stage 4 breast cancer diagnosis and the path that led her to explore integrative cancer care. Chelsea discovered a lump shortly after turning 40 and was quickly diagnosed with HER2-positive breast cancer that had metastasized to her liver. Within weeks, she began chemotherapy and entered the world that so many people with cancer know well. As she moved through treatment, Chelsea began researching other approaches that might support her body and improve how she felt during therapy. That curiosity eventually led her to the Hope For Cancer treatment centers, where she explored non-invasive therapies such as hyperbaric oxygen, hyperthermia, ozone therapy, and nutrient infusions as part of an integrative program. In this conversation, Laura and Chelsea discuss the fear many patients feel when considering integrative care, the importance of asking questions, and why finding a treatment path that aligns with your values and intuition can be an important part of the healing journey. This episode shares Chelsea's story and the insights she gained along the way.   Resources Mentioned: Work with Laura: https://www.thebreastcancerrecoverycoach.com/health  Follow Chelsea: https://www.instagram.com/hassink_health_bites/ Hope For Cancer Centers: https://hope4cancer.com/     Let's Connect! If this episode helped you breathe a little easier, please share it with a friend or leave a review. Every share helps spread this message of hope, healing, and whole-person wellness.

In this new episode of Speaking of SurgOnc, Dr. Rick Greene & Dr. Jamie Rand discuss the article: Omission of Axillary Lymph Node Dissection in Patients with pT0-2 ER+/HER2− Breast Cancer with 3–5 Positive Lymph Nodes Undergoing Adjuvant Systemic Therapy and Radiation Does Not Impact Overall Survival: A Cancer Database Analysis, from the February 2026 issue of the Annals of Surgical Oncology.

Drs. Isaacs and Traina review how HER2CLIMB‑05 and PATINA challenge the old CLEOPATRA‑based approach by showing that adding tucatinib or palbociclib to maintenance therapy can extend progression‑free survival in metastatic HER2+ breast cancer. They stress tailoring maintenance regimens to each patient's hormone receptor status, CNS risk, and tolerance for side effects.

Send a textWhat do the latest findings from the 2025 San Antonio Breast Cancer Symposium mean for people living with metastatic breast cancer? In this episode, Dr. Bora Lim of MD Anderson Cancer Center joins us to break down the most impactful research and clinical trial updates from SABCS 2025. Together we will explore advances in hormone receptor positive, HER2-positive disease and triple negative disease and discuss how these updates may influence treatment decisions right now. We also wrap up with an audience Q&A, including questions about GLP-1 medications.Listen in for expert insight, practical takeaways, and clarity on the evolving MBC treatment landscape.

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

Nancy and Shelley didn’t plan to share a breast cancer story, much less two very different diagnoses, eight years apart. One faced Stage 0 DCIS at 41 after pushing for a 3D mammogram; the other walked into an annual screening, felt no lump, and still heard “Stage 2 HER2‑Positive.” In this conversation, we talk about what happens when two pragmatic, organized women lean on faith, friendship, and their networks to move fast on treatment—then turn around and use their experience to champion The Rose and the women who rely on us for access to mammograms, diagnostics, and compassionate care. Please consider sharing this episode, or making a donation at therose.org so more women receive breast cancer screening and care. Subscribe to Let’s Talk About Your Breasts on Apple Podcasts, Spotify, iHeart, and wherever you get your podcasts. Key questions answered How did Nancy and Shelley each grow up with service and volunteering, and how did that shape their careers and philanthropy? What kind of work do they do in the plastics industry, and how did Shelley end up co‑inventing a “tiltless” liner used around the world? How did Shelley’s first 3D mammogram at 41 lead to a stage zero DCIS diagnosis, and why did she struggle to call it “cancer”? What made Nancy’s diagnosis different—stage two HER2‑positive with no lump—and how did prior research for Shelly help her move quickly? How did Nancy’s long history of volunteering and relationships at Baylor help both mother and daughter fast‑track appointments and treatment? What do they mean by “God winks,” and how did shared surgeons, the same radiologist, and overlapping timelines reinforce their faith? In what ways did cancer deepen—rather than define—their mother–daughter relationship and cement that “best friends” dynamic? How do they each use their stories now to push friends, colleagues, and even their kids to prioritize mammograms and routine screenings? Why is The Rose the organization they chose to champion, and how do insured patients’ mammograms help cover care for uninsured and underinsured women? What do they want listeners to understand about the emotional side of bell‑ringing, being present for each other, and never being “too busy” to schedule preventive care? Timestamped overview 03:20 Welcoming Nancy and Shelley as Everything’s Coming Up Roses honorees; their shared background as successful women in male‑dominated plastics and lifelong volunteers. 07:20 Nancy’s early volunteer roots, decades with arts and civic groups, current work with the Greater Houston Women’s Chamber of Commerce, and Shelley’s career in plastics—including her patented tiltless liner and global travel as a family. 10:00 The “backwards” breast cancer story: Shelley’s stage zero DCIS diagnosis at 41 after pushing for a 3D mammogram, her embarrassment about calling it cancer, and the lack of family history aside from an elderly grandmother. 14:30 Nancy’s 2023 diagnosis: annual mammogram, no lump, stage two HER2‑positive, choosing a world‑class oncologist, and how watching Shelley’s calm, research‑driven approach prepared her. 18:30 How Nancy’s Baylor relationships and volunteer network helped both women move quickly through diagnosis and into treatment; the shared focus on reducing the stress of “waiting” and the role of faith in that season. 22:30 “God winks”: both having the same surgeon, Shelley’s husband later sharing her radiologist, and the reminder that—even for highly organized women—God is still in control. 26:30 How their faith kept them from seeing cancer as punishment, why they refused to play the victim, and how the experience tightened their bond without defining their identities. 31:10 Bell‑ringing surprises: Nancy showing up for Shelley’s bell, Shelley returning the favor and scaring her mom in the parking lot, and how those moments became treasured markers in their journey. 32:44 Using their platform: encouraging others to schedule mammograms, explaining how insured patients at The Rose help fund care for uninsured women, and embracing their “backwards” mother–daughter honoree role to amplify The Rose’s mission and make sure no woman walks around not knowing help is available.See omnystudio.com/listener for privacy information.

Drs. Isaacs and Traina discuss new data in HER2+ breast cancer from the 2025 San Antonio Breast Cancer Symposium, focusing on early-stage studies including DESTINY-Breast11 and DESTINY-Breast05 and how data from these studies could potentially impact patient care in the future.

Do you know how many different types of anti-HER2 therapies are in clinical trials for gastroesophageal adenocarcinoma (GEA)? Credit available for this activity expires: 02/27/2027 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/breaking-ground-gastroesophageal-adenocarcinoma-first-line-2026a10005tj?ecd=bdc_podcast_libsyn_mscpedu

Drs. Cytryn, Foote, and Thummalapalli discuss recent data on HER2 testing modalities and the prevalence of HER2 positivity across hepatobiliary, upper GI, and colorectal cancers, highlighting implications for precision medicine. The conversation reviews the latest clinical trial findings and the evolving landscape of HER2-targeted therapies, with insights into optimal treatment sequencing for various GI cancer subtypes.

Dr. Lakshmi Rajdev and Dr. Manish Shah join the podcast to discuss the updated guideline on immunotherapy and targeted therapy in unresectable locally advanced, advanced, or metastatic gastroesophageal cancer. They share first-line and subsequent-line recommendations for both gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma based on actionable biomarkers including PD-L1 expression, MMR and/or MSI, CLDN18.2 expression, and HER2 status. They note the importance of the algorithms and tables in the guidelines that provide visual illustrations and quick reference guides of the evidence-based recommendations. They also comment on ongoing and recently presented trials that may impact future guidelines in this space. Read the full guideline, "Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update" at www.asco.org/gastrointestinal-cancer-guidelines" TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/gastrointestinal-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology,  https://ascopubs.org/doi/10.1200/JCO-25-02958      Timestamps ·       00:00 – 02:15 Introduction and Overview ·       02:16 - 08:20 First-line treatment for patients with pMMR/MSS, HER2-negative gastroesophageal adenocarcinoma ·       08:21 –10:29 First-line treatment for patients with pMMR/MSS, HER2-positive gastroesophageal adenocarcinoma ·       10:30 – 14:39 First-line treatment for patients with dMMR/MSI-H, gastroesophageal adenocarcinoma ·       14:40 – 18:03 First-line treatment for ESCC ·       18:04 – 22:04 Second- and third-line therapy for gastroesophageal adenocarcinoma and ESCC ·       22:05 – 24:38 Importance of guideline ·       24:39 – 27:45 Outstanding questions and future research   Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey, and today I am interviewing Dr. Lakshmi Rajdev from the Icahn School of Medicine at Mount Sinai and Dr. Manish Shah from Weill Cornell Medicine, co-chairs on "Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update." Thank you for being here today, Dr. Rajdev and Dr. Shah. Dr. Lakshmi Rajdev: Thank you. Dr. Manish Shah: Thank you for having us. It is wonderful. Brittany Harvey: And then just before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Rajdev and Dr. Shah, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then to dive into what we are here today to talk about, Dr. Shah, I would like to start first with what prompted the update to this guideline, which was previously published in 2023, and what is the scope of this updated guideline? Dr. Manish Shah: Yes, terrific. So even in the last few years, the pace of drug development in gastroesophageal cancers has just been astounding. So, what prompted this guideline is actually the practice-changing results for a new biomarker, CLDN18.2 hat was based on the GLOW and SPOTLIGHT studies, as well as a practice-changing study in HER2-positive disease where we added pembrolizumab to trastuzumab and chemotherapy for tumors that are HER2-positive and PD-L1 CPS 1 or greater. And then there were also new studies and new approvals in esophageal squamous cell cancer that you will hear about as well. So there were several studies, overall more than 5,000 patients were reported on, and that led to several new therapies, new indications, and it really necessitated this guideline. Brittany Harvey: Excellent. It is great to hear about all of these exciting updates in this space. So then to next review the key recommendations of this guideline by clinical question that the expert panel addressed. So, Dr. Rajdev, what is the recommended first-line treatment for patients with proficient mismatch repair, microsatellite stable, HER2-negative gastroesophageal adenocarcinoma? Dr. Lakshmi Rajdev: Thank you for that question. So historically, we have sort of used fluoropyrimidine and platinum doublets, which yielded a survival of about one year. More recently, immunotherapy and targeted therapy options have improved outcomes in patients with advanced esophageal and gastric adenocarcinoma, as well as squamous cell carcinoma. Patients with gastric and GE junction adenocarcinoma have a high rate of actionable alterations, so it is imperative that physicians test the following biomarkers upfront so that it can help guide therapy. The markers recommended by the ASCO panel are HER2, MMR or MSI, CLDN18.2, and PD-L1. And also, it was recommended to use NGS if feasible in this patient population. HER2, as we know, is expressed in about 15% to 25% of patients; PD-L1 expression occurs in about 80% of patients; MSI-high, deficient MMR is present in about 5% to 8% of patients; and CLDN18.2 expression is present in about 40% of patients. There is, of course, biomarker overlap. About 13% to 22% of CLDN18.2 patients are also PD-L1 positive. For patients with pMMR or microsatellite stable HER2-negative disease with PD-L1 expression greater than 1 and absence of CLDN18.2, the panel recommended a first-line therapy with fluoropyrimidine and platinum-based therapy in combination with immunotherapy. These recommendations stem from large phase 3 trials, and the agents approved in the United States are pembrolizumab, nivolumab, and tislelizumab. It has been shown that immunotherapy benefit is greater in patients with higher PD-L1 expression, and it is not possible to comment on the individual PD-L1 cutoff scores and sort of identify the optimal PD-L1 cutoff score that sort of balances benefits and harms. But what is recommended is that immunotherapy-based treatments can be offered in patients with a CPS score of greater than 1. With regard to the choice of immunotherapy agents, that is pembrolizumab, nivolumab, or tislelizumab, these agents are considered to have similar efficacy, and the selection of an agent could be based on dosing schedule, cost considerations, toxicity, and the method of administration. Typically, clinicians should avoid withholding the start of chemotherapy while awaiting biomarker testing, depending on the clinical scenario. Now, for patients with pMMR microsatellite stable disease that is HER2-negative with PD-L1 expression less than 1 and positive CLDN18.2 expression, zolbetuximab-based treatments or in combination with chemotherapy is recommended, and this is based on two global phase III randomized controlled trials, the GLOW and the SPOTLIGHT. And across both studies, the hazard ratio for the overall survival was 0.78, and similarly, there was also an improvement in progression-free survival favoring the zolbetuximab group compared to the chemotherapy group alone. An important note is that nausea, vomiting is commonly associated with zolbetuximab-based treatments, and the panel recommended prophylactic antiemetics, adjusting zolbetuximab infusion rates, pausing infusion temporarily, using non-prophylactic antiemetics, and hydration intravenously prior to discontinuation of zolbetuximab-based chemotherapy. So effective handling of the GI-related symptoms with zolbetuximab is recommended prior to discontinuation of therapy. Now, for patients with pMMR microsatellite stable HER2-negative gastric, GE junction adenocarcinoma with PD-L1 expression greater than 1 and CLDN18.2 positivity, the ones with the dual expression with CLDN18.2 as well as PD-L1 chemotherapy, the choice of therapy can be based on the degree of PD-L1 expression, the toxicity profile, the burden of symptoms, and the anticipated improvement in symptoms associated with response to treatment, the patient comorbidities, the prior medical and treatment history. So this decision needs to be made on a case-by-case basis, and these are some of the factors that we suggested that could potentially influence the choice of therapy. For patients with pMMR microsatellite stable disease that is HER2-negative and a PD-L1 expression less than 1 and an absence of CLDN18.2 expression, first-line therapy with fluoropyrimidine and platinum-based chemotherapy is recommended. So you can see we have segmented out patients based on PD-L1 expression, pMMR and microsatellite stable disease expression, and also based on CLDN expression. Brittany Harvey: Absolutely. And that first point you noted, I think is really important, that biomarker testing is really critical for treatment decision-making in this space. So then the next subgroup of patients that the panel looked at, Dr. Shah, what first-line therapy is recommended for patients with proficient mismatch repair, microsatellite stable, HER2-positive gastroesophageal adenocarcinoma? Dr. Manish Shah: So this was an update from a few years ago. So we have known for 15 years now that if you are HER2-positive, you should get trastuzumab plus chemotherapy. That was based on the ToGA trial. And the update now is based on a trial called KEYNOTE-811, where it examined the addition of pembrolizumab to trastuzumab and chemotherapy versus trastuzumab and chemotherapy, and there was a progression-free and overall survival benefit. And again, here, the biomarkers are important. If your CPS PD-L1 is less than 1, we would not recommend Pembrolizumab in that setting, so you would still get trastuzumab and chemotherapy. But if it is 1 or greater, the PD-L1 CPS score, then we do recommend pembrolizumab unless there is a contraindication to immunotherapy. The take-home message really is from the onset of diagnosis, please check your biomarkers. And I will just, it is worth repeating, it is important to check your PD-L1 status, HER2 status, mismatch repair status, and CLDN18.2 status. And then the optimal therapy, and it is outlined in the publication, is really biomarker-driven. We know that if we are able to hit the target that is overexpressed, we are going to have a better outcome. And Dr. Rajdev did mention where there is overlap, there can be a lack of data, and that is where we are with both PD-L1 positive and CLDN positive. Here we do have data in HER2-positive cases where if you are both HER2-positive and PD-L1 positive, you would combine trastuzumab and pembrolizumab for the best outcomes. Brittany Harvey: Understood. I really appreciate you detailing what is most important for each individual biomarker combination that patients may have. So then following that, Dr. Rajdev, what does the expert panel recommend for first-line treatment for patients with esophageal squamous cell carcinoma that is not amenable to definitive chemoradiation? Dr. Lakshmi Rajdev: There are three phase III randomized clinical trials that have influenced practice in patients with esophageal squamous cell carcinoma examining the benefit of immunotherapy in this patient population. The RATIONALE-306 was a randomized trial of tislelizumab plus chemotherapy with platinum and fluoropyrimidine or paclitaxel versus placebo with chemotherapy. And then you have the KEYNOTE-590, which compared pembrolizumab plus chemotherapy versus chemotherapy alone. And then you have CheckMate-648, which included comparisons of nivolumab plus chemotherapy versus nivolumab plus ipilimumab or chemotherapy. And the primary endpoints for these studies were overall survival, and they did look at subgroups with PD-L1 expression. They used TPS score greater than 1% in CheckMate-648 and PD-L1 CPS greater than 10 in KEYNOTE-590. The bottom line is that the overall hazard ratio for overall survival across this patient population was 0.72. So clearly, there is benefit in patients that express PD-L1 CPS greater than 1 for benefit for the addition of immunotherapy. Now, the benefit again in patients with a PD-L1 expression less than 1 remains limited, and so the panel has made a recommendation for using immunotherapy in combination with platinum-based chemotherapy in patients with a PD-L1 greater than 1. Again, we know that it is hard to make recommendations on what PD-L1 cutoffs are recommended in this patient population, meaning that should it be limited to patients with a PD-L1 of 1 to 4 or greater than 10? I think that the general consensus that has been gleaned from the data is that the higher the PD-L1 expression, the greater the benefit. I do want to comment on another option that is available in patients with squamous cell carcinoma compared to adenocarcinoma, and that is the combination of nivolumab and ipilimumab. Now, in CheckMate-648, nivolumab with ipilimumab was also recommended as a treatment option in patients that have a PD-L1 score of greater than 1. There was a survival benefit demonstrated with this combination compared to chemotherapy alone. And an important observation in this study is that, although there was a slightly increased rate in early death, but there was really no significant difference in PFS and OS compared to chemotherapy alone. Importantly, the treatment appeared to be pretty well tolerated by the study population. There was a notable difference in the objective response rate, which was 35% in the nivolumab plus ipilimumab group compared to patients receiving nivolumab and chemotherapy, where it was 53%. So superiority is, so the importance of chemotherapy in patients with esophageal squamous cell carcinoma is to be noted. However, there is no difference in overall survival and progression-free survival when using the combination of nivolumab and ipilimumab, and thus it affords a chemotherapy-free option for this patient population with esophageal squamous cell carcinoma and a CPS with a score of greater than 1. Brittany Harvey: Understood. I appreciate you reviewing the evidence underpinning those recommendations as well. So then the next patient population that the guideline panel addressed, what first-line therapy is recommended for patients with deficient mismatch repair, microsatellite instability-high, gastroesophageal adenocarcinoma or esophageal squamous cell carcinoma? Dr. Lakshmi Rajdev: The rate of MSI-high expression is about 3% to 7% across different studies. Now, the KEYNOTE-158 was a tumor-agnostic study in patients with non-colorectal cancers, and again, the problem with the MSI-high population, given that it is so rare, the numbers in the individual studies are fairly small. But consistent outcomes do emerge, indicating high response to immunotherapy. So in KEYNOTE-158, a response rate of about 46% was noted. The number of patients was small, it was about 24. In CheckMate-649, which is a study of chemotherapy plus or minus nivolumab in patients with advanced gastric adenocarcinoma, there was again a very small number of patients, and patients that were MSI-high or deficient MMR did experience substantial benefits with the addition of immunotherapy, with hazard ratios in the order of about 0.38. In KEYNOTE-062, again, it was a very small number of patients, again about 6% or so, and similar to CheckMate-649, a substantial benefit was noted in combination with chemotherapy, but also there were benefits noted with pembrolizumab alone. The RATIONALE-305 again was a study of tislelizumab in combination with chemotherapy and similarly showed benefits to the combination of chemotherapy plus immunotherapy in this patient population. I think that we are all aware of the dramatic benefits of immunotherapy in this particular subset of patients, deficient MMR MSI-high, and also we have seen in CheckMate-649 they did have a subset of patients that received nivolumab and ipilimumab. And in this patient population, they noted unstratified hazard ratio of 0.28. So I think that the overall consensus is that immunotherapy is a very important treatment modality in patients with deficient MMR MSI-high disease, given that a lot of the trials in gastroesophageal adenocarcinoma have utilized chemotherapy-based options, that is certainly a recommendation of the panel to use chemotherapy in combination with immunotherapy. However, on a case-by-case basis, the panel recommended immunotherapy alone as well, and given the high response rates noted in trials across different diseases as well as noted in this disease as well. Brittany Harvey: Certainly. And I appreciate you both for reviewing these first-line recommendations. So moving to later lines of therapy, Dr. Rajdev, what recommendations did the expert panel make for second or third-line therapy for gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma? Dr. Lakshmi Rajdev: So, I think that the RAINBOW trial that investigated the utility of the addition of ramucirumab as second-line therapy has been around since 2014, and those results have led to the addition of ramucirumab to taxane-based therapy in the second-line setting. Based on the utilization of oxaliplatin and platinum-based therapy in the front-line setting, there may be patients that have an underlying neuropathy, and so we wanted to really include treatment options for this patient population so that an agent that is less neurotoxic could also be recommended in combination with ramucirumab. The RAMIRIS trial is one such trial where ramucirumab was combined with FOLFIRI, and it demonstrated benefit in combination with ramucirumab. So we have listed that as a potential treatment option for patients in the second-line setting who may have an underlying neuropathy or even for whatever reason that based on the toxicity profile, that needs to be the preferred option by a physician, that recommendation is new from the older guidelines that we have. With regard to the utility of PD-1 inhibitors, there really has been no benefit noted in the second-line setting with regard to overall survival or progression-free survival, so no recommendation is made for that option. I think an important study that has been recently presented is the DESTINY-Gastric04 trial, which really has been practice-changing and has led to the recommendation for trastuzumab deruxtecan in patients that have HER2-positive metastatic gastric or GE junction adenocarcinoma. Now, this is a phase III trial in patients who retained HER2-positive disease after progressing on front-line trastuzumab-based treatments, and the comparator for this trial was trastuzumab deruxtecan versus ramucirumab plus paclitaxel. There was significant improvement and progression-free survival in patients that received trastuzumab deruxtecan. The patients that were excluded from the trial are patients that have pulmonary problems, interstitial lung disease; that is one of the toxicities of this particular agent, and close monitoring and prompt initiation of therapy such as glucocorticoid treatment in patients who develop this toxicity was also highlighted by the panel. So to summarize, the new guidelines highlight the possibility of FOLFIRI plus ramucirumab as a second-line option and then trastuzumab deruxtecan as a later-line option in patients that still retain HER2 expression. And that is very important because the trial did retest patients whether they expressed HER2. As we know, in a substantial number of patients, there is downregulation of HER2, and there is emerging data that the benefit for subsequent HER2-directed therapies is best noted in patients that still retain HER2 expression. Brittany Harvey: Great. So as our listeners have heard, there are many recommendations and new treatment options for advanced gastroesophageal cancer. Dr. Shah, earlier you highlighted the importance of biomarker testing, but I would like to hear in your view, what is the importance of this guideline and how will it impact both clinicians and patients with gastroesophageal carcinoma? Dr. Manish Shah: So as we have discussed throughout this podcast, the treatment for gastroesophageal cancer, both adenocarcinoma and squamous cell cancer, is increasingly complex, increasingly biomarker-driven. And I think the value of the guideline is to place all of that into context. So it provides the data for why certain biomarkers are important, what therapies should be indicated. Not only that, but if you are able to review the guideline, it provides the details of each of these studies and summarizes them in a meta-analysis fashion to sort of give you the context, because sometimes the individual studies can be maybe a little bit discordant or confusing and the guideline attempts to harmonize all that. And then also, I think the tables are very, very interesting because they give you actual numbers in terms of how many patients over a thousand would this benefit or how many patients over a thousand would this cause harm in terms of nausea, vomiting, or other things like that. So it gives you context for helping clinicians and patients weigh the potential benefits of the novel treatment strategies against the potential adverse events. And then finally, the guideline does also provide an algorithm that you are able to follow based on the biomarkers, and those are in figures 4 and 5. So I think overall, it is a very comprehensive guideline. It intends to make more manageable a very complex subject, and you know, I really encourage our listeners to review it after listening to the podcast. Dr. Lakshmi Rajdev: If I can add to that, I think that what is also really good about the guidelines is there are quick summaries. So if someone is busy in the clinic, of course, there is the opportunity to review the data supporting the guidelines in great depth in the manuscript, but what is also really good is that there are good summaries. In the event that you are very busy, you can easily identify what the recommendations should be for that particular patient based on these summaries. Brittany Harvey: Absolutely. Listeners are encouraged to review the full guideline, including those tables and figures that may be more helpful when they are looking for something quick to look at in the clinic as well. So, as you both mentioned, there have been a number of recent practice-changing trials in this area. So I imagine there is still a lot of ongoing research as well. So Dr. Shah, what are the outstanding questions regarding treatment options for patients with locally advanced unresectable, advanced, or metastatic gastroesophageal carcinoma? Dr. Manish Shah: I think we touched upon it a little bit. The guidelines are based on the data available, and they are primarily examining one novel therapy with chemotherapy in a specific biomarker population. But as you know, the biomarkers are not either/or; you are not either CLDN18.2 positive or PD-L1 positive. A portion of patients could have dual biomarkers, and you know, I think that we are generating data on how to manage those patients. At the recent GI Symposium in January this year, the ILUSTRO trial was presented by Dr. Shitara, which looked at combining zolbetuximab and chemotherapy with immunotherapy for dual-positive biomarkers, and that is leading to a phase III study that has begun to enroll. So unanswered questions are: how do we manage dual-positive biomarkers? The other thing that was mentioned is that the current data for mismatch repair deficiency involve chemotherapy plus immunotherapy. Only squamous cell cancer is there a study with a positive non-chemotherapy kind of backbone, that is CheckMate-648 that Dr. Rajdev mentioned. As we move forward, it will be good to get data on non-chemotherapy options in certain biomarker-positive populations. And then finally, another update, which is likely to be practice-changing, is the HERIZON-GEA-01 study that looked at zanidatamab, which is another biparatopic antibody that targets HER2, and that is likely to change practice. And as that data gets published, we may look to even do a rapid update for the current immunotherapy and targeted therapy guideline that is just being published. Dr. Lakshmi Rajdev: So, if I can add to that, there are numerous ADCs that look very interesting. There are bispecific antibodies; in fact, the zanidatamab is a bispecific antibody showing improved activity in patients with HER2-positive disease. So I think there are studies from Asia looking at CLDN CAR T-based therapies. So, I think that there are a lot of novel agents and a lot of excitement in the field. We know that the bemarituzumab study, unfortunately, the FGFR2 inhibitor failed to demonstrate any benefit, but I think that there are other agents that are being explored, so there are newer targets, newer agents, ADCs, bispecifics that could potentially change the field in the future. Brittany Harvey: Yes, we will look forward to the data to address these unanswered questions and new agents and inform future guideline updates. So, I would like to thank you both for all of your work to review the evidence here and update this important guideline, and for your time today, Dr. Rajdev and Dr. Shah. Dr. Lakshmi Rajdev: Thank you. Dr. Manish Shah: Thank you. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

This week, we explore a new standard of care for high-risk HER2-positive early breast cancer, long-acting therapy for people with HIV facing adherence challenges, a first-in-class trial of a p53 reactivator, and tecovirimat for mpox. We review group B streptococcal disease and a revealing case of prosthetic joint infection. Perspectives examine the role of folate therapy, Medicare drug-price negotiation, AI in medical education, and incidental findings.

In this episode of the Oncology Brothers podcast, we dived deep into the evolving landscape of HER2-positive breast cancer treatment following the significant advancements made in 2025. Joined by Dr. Virginia Kaklamani from UT Health San Antonio, we discussed the latest data from SABCS 2025 and pivotal trials such as DESTINY-Breast09, which have led to new treatment approvals and strategies. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Key topics included: • The treatment algorithm for early-stage HER2-positive breast cancer, including the APT trial and the role of trastuzumab. • Insights into neoadjuvant and adjuvant therapies, including the implications of the neoCARHP trial regimen and the potential of T-DXd. • The impact of recent studies in metastatic HER2-positive disease, including the approval of T-DXd plus pertuzumab and the promising results from the PATINA trial. • A discussion on managing side effects and the importance of patient quality of life during treatment. Join us for an informative conversation that highlights the latest advancements in HER2-positive breast cancer care and how they can be applied in clinical practice. Don't forget to like, subscribe, and leave a review to help us reach more healthcare professionals who can benefit from these discussions! #HER2Positive, #BreastCancer, #SABCS25, #TDXd, #BreastCancerTreatment, #OncologyBrothers

Swedish biotech Affibody has spent over two decades engineering proteins 1/20th the size of a conventional monoclonal antibody — and CEO David Bejker believes they're perfectly suited to solve one of radioligand therapy's biggest problems: a dangerously narrow target space. Bejker discusses how Affibody's platform combines the selectivity of antibodies with the biodistribution flexibility of small molecules, the science behind its Albumod technology, and how its HER2 imaging and therapeutic programs are translating from animals to humans. He also digs into partnerships with AstraZeneca's respiratory unit and complement-focused Rally Bio, manufacturing advantages of E. coli-based production, and Affibody's long-term ambitions as a commercial-stage company.

Cristina Saura Manich, MD, PhD - First-Line Treatment of HER2-Positive Metastatic Breast Cancer: Could Investigational Approaches Improve on Current Standard of Care?

In this JCO Precision Oncology Article Insights episode, host Dr. Carolyn Lineen summaries the article, "Concordance of Oncotype DX Breast Recurrence Score Assay Results Between Paired Core Needle Biopsy and Surgical Excision Specimens in Hormone Receptor Positive, HER2-Negative Early-Stage Breast Cancer," by Nassar et al. TRANSCRIPT Carolyn Lineen: Hello and welcome to JCO Precision Oncology Article Insights. I'm your host, Carolyn Lineen, from St. James's Hospital, Dublin, and today we will be discussing the JCO Precision Oncology article titled "Concordance of Oncotype DX Breast Recurrence Score Assay Results Between Paired Core Needle Biopsy and Surgical Excision Specimens in Hormone Receptor Positive, HER2-Negative Early-Stage Breast Cancer" by Dr. Aziza Nassar and colleagues. The Oncotype DX Breast Recurrence Score assay is a 21-gene expression test that provides both prognostic information regarding distant recurrence risk and predictive information regarding the benefit of adjuvant chemotherapy in hormone receptor-positive, HER2-negative early-stage breast cancer. The recurrence score ranges from 0 to 100, with higher scores indicating a greater risk of recurrence and a potentially higher likelihood of benefit from chemotherapy. Traditionally, genomic testing is performed on surgical excision specimens following tumor resection. However, this approach can potentially delay access to biological risk stratification, which may be important when early treatment planning or neoadjuvant therapy is being considered. The primary objective of this study was to evaluate the level of concordance between recurrence scores derived from paired core needle biopsy specimens and surgical excision specimens obtained from the same untreated primary breast tumors. Investigators specifically evaluated both continuous recurrence score agreement and categorical risk classification concordance. The study included 134 patients with paired biopsy and surgical specimens. The median patient age was 62 years, with a wide age range from 33 to 99 years. Approximately 17% of patients were aged 50 years or younger, while 83% were older than 50 years. All patients had hormone receptor-positive, HER2-negative early-stage breast cancer and had not received prior systemic treatment before either specimen collection. Each patient contributed two tumor samples: a core needle biopsy specimen obtained at initial diagnosis and a surgical excision specimen obtained during definitive tumor resection. Both samples underwent Oncotype DX testing, allowing direct within-patient comparison. The investigators reported mean recurrence scores of 15.6 for core needle biopsy specimens and 16.6 for surgical excision specimens. Although this absolute mean difference between specimen types did reach statistical significance with a P value of 0.003, the authors note that this numerical difference was small at one recurrence score unit and may not therefore be clinically meaningful. Additionally, categorical recurrence score results did not differ significantly. The primary measure of agreement between recurrence scores was the Lin's concordance correlation coefficient. The study demonstrated a Lin concordance correlation coefficient of 0.86 with a 95% confidence interval ranging from 0.80 to 0.90, indicating strong agreement between biopsy and surgical specimens. Additionally, categorical agreement was assessed using Cohen's kappa statistic. The study reported a kappa value of 0.64 with a 95% confidence interval from 0.44 to 0.83, indicating substantial agreement between specimen types. Comparing this study to previously published evidence, the authors referenced prior smaller studies examining concordance between paired tissue samples. For example, earlier research evaluating 50 patients demonstrated correlation coefficients of approximately 0.8 and categorical concordance rates ranging from 72% to 78%, depending on the classification cut points used. Compared with earlier studies, the present study provides stronger evidence supporting consistency between biopsy and surgical testing. These findings have several important implications for clinical practice. First, early availability of recurrence score results may enhance multidisciplinary care planning. Obtaining genomic risk data at the time of diagnosis allows tumor boards to integrate molecular risk stratification into initial treatment discussions rather than waiting for postoperative results. Second, biopsy-based testing may support decision making regarding treatment sequencing. Earlier genomic information may help guide selection of neoadjuvant therapy or inform early decisions about adjuvant chemotherapy necessity. Third, early testing may reduce delays in treatment initiation. Separate research evaluating presurgical Oncotype DX testing has demonstrated potential reductions in time to initiation of adjuvant therapy by approximately 8 days, suggesting potential improvements in care efficiency. Additionally, biopsy-based testing demonstrates strong technical feasibility. Studies examining real-world implementation have reported test success rates as high as 99.1% when performed on core biopsy specimens. Despite the encouraging results, certain limitations must be considered. Core needle biopsy samples evaluate only a portion of the tumor, and intratumoral heterogeneity could theoretically influence recurrence score results in selected cases. Preanalytical factors, including tissue fixation and sample handling, may also affect RNA integrity and assay performance. Standardization of specimen processing protocols will be essential if biopsy-based testing becomes routine. Furthermore, although analytical concordance is strong, prospective outcome studies demonstrating equivalent long-term clinical outcomes based on biopsy-directed treatment decisions would further strengthen the evidence base. In conclusion, this study demonstrates strong concordance between Oncotype DX Breast Recurrence Scores derived from core needle biopsy specimens and surgical excision specimens in patients with hormone receptor-positive, HER2-negative early-stage breast cancer. With a concordance correlation coefficient of 0.86 and overall categorical agreement exceeding 90%, the findings support the clinical feasibility of performing genomic testing at the time of diagnostic biopsy. If validated through additional prospective studies, this approach may enable earlier risk stratification and improve multidisciplinary treatment planning. Thank you for tuning in to JCO Precision Oncology Article Insights. Don't forget to subscribe and join us next time as we explore more groundbreaking research shaping the future of oncology. 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.

Cristina Saura Manich, MD, PhD - First-Line Treatment of HER2-Positive Metastatic Breast Cancer: Could Investigational Approaches Improve on Current Standard of Care?

Cristina Saura Manich, MD, PhD - First-Line Treatment of HER2-Positive Metastatic Breast Cancer: Could Investigational Approaches Improve on Current Standard of Care?

Cristina Saura Manich, MD, PhD - First-Line Treatment of HER2-Positive Metastatic Breast Cancer: Could Investigational Approaches Improve on Current Standard of Care?

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/WWQ865. CME/MOC/NCPD/AAPA/IPCE credit will be available until February 12, 2027.TROP2-Targeting ADCs in the Forefront: Changing Standards and Best Practices in TNBC and HR+, HER2- Breast Cancer Care In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Gilead Sciences, Inc.Disclosure information is available at the beginning of the video presentation.

Sarah Poland, MD, lead author of a recently published article in the journal ONCOLOGY titled Advances in Immunotherapy for Breast Cancer, highlighted key findings from her review in a conversation with CancerNetwork®.1 Throughout the discussion, she spoke about: Shifting Perspectives on Immunogenicity: Historically, breast cancer was considered a “cold,” poorly immunogenic tumor due to low tumor mutational burden (TMB) and few tumor-infiltrating lymphocytes (TILs). Poland highlighted how clinical research has shifted this perspective, particularly through the study of triple-negative breast cancer (TNBC), which often exhibits higher PD-L1 expression and immune infiltration.Key Clinical Milestones: The review highlighted foundational data that established immunotherapy as a standard of care: Early-Stage TNBC: The phase 3 KEYNOTE-522 trial (NCT03036488) established pembrolizumab (Keytruda) plus chemotherapy as a standard neoadjuvant treatment for stage II to III TNBC.2 Metastatic TNBC: The phase 3 KEYNOTE-355 trial (NCT02819518) demonstrated the benefit of pembrolizumab in PD-L1–positive metastatic disease.3 Managing Toxicity and Rechallenge: Poland addressed the feasibility of pembrolizumab rechallenge after an immune-related adverse effect (irAE), emphasizing that while possible, it requires a highly individualized approach based on the severity and timing of the initial toxicity.The Future Landscape: Beyond PD-1/PD-L1 inhibitors, the discussion covered emerging technologies that are poised to redefine treatment: Antibody-Drug Conjugates (ADCs): Exploration of novel combinations of ADCs with immunotherapy. Emerging Modalities: The potential role of bispecific antibodies and vaccine trials utilizing tumor antigens. Subtype Expansion: Emerging evidence supporting the efficacy of immunotherapy in hormone receptor–positive and HER2-positive subtypes, moving beyond the traditional focus on TNBC. Unmet Educational Needs: Poland emphasized the importance of resources that connect providers and patients, particularly in translating complex trial data into clinical practice and addressing patient concerns regarding the newest therapies and trials.Poland is from the Department of Medicine in the Section of Hematology/Oncology at The University of Chicago.References1.        Poland S, de Oliveira Andrade M, Nanda R. Advances in immunotherapy for breast cancer. Oncology (Williston Park). 2026;40(1):8-15. doi:10.46883/2026.259210612.        Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa19105493.        Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217-226. doi:10.1056/NEJMoa2202809

Send a textWhat actually needs to be in place before digital pathology can replace the microscope?In this episode of DigiPath Digest, I walk through the 2026 Polish Society of Pathologists guidelines and translate them into practical steps for real pathology labs. This isn't theory. It's about hardware fidelity, data integrity, validation, and AI integration — and what each of these actually requires in daily workflow.We talk about scanner resolution standards (≤0.26 μm per pixel), 4K monitor calibration, visually lossless compression (20:1), scalable storage, pathologist-driven validation, and what “non-inferiority” truly means.Digital pathology is not just a change of medium. It's an operational shift.Episode Highlights[00:02] Community & growth 1,600+ new newsletter subscribers, 10,000+ Facebook members, and free Digital Pathology 101 book access.[07:20] The 4 pillars of adoption Hardware fidelity · Data integrity · Clinical validation · Future integration.[08:30] Hardware requirements 40x equivalent scanning (≤0.26 μm/px), 4K monitors, >300 cd/m² luminance, 10-bit color depth.[12:00] Workflow & throughput 200–300 slides/day per scanner, automated focus control, urgent case prioritization.[17:25] Storage & archiving ~1 GB per slide. Active archive (6–24 months). Long-term retention (10–20 years). GDPR compliance & TLS encryption.[23:09] Validation philosophy Pathologist-centered validation. Two phases: • Familiarization (~20 retrospective cases) • Dual review with discrepancy tracking Goal: digital must be non-inferior to glass.[29:03] AI in digital pathology AI supports quantification (Ki-67, HER2, ER/PR, PD-L1), tumor detection, and future multimodal predictions — but pathologists remain central.[33:26] Intraoperative telepathology

Please visit answersincme.com/CZS860 to participate, download slides and supporting materials, complete the post test, and get a certificate. Presented by Giuseppe Curigliano, MD, PhD. In this activity, an expert in oncology discusses the differentiation of patients with HER2-low/ultralow/negative advanced breast cancer and treatment with antibody-drug conjugates. Upon completion of this activity, participants should be better able to: Differentiate HER2-low, -ultralow, and -negative advanced breast cancer; Identify patients with HER2-low and -ultralow advanced breast cancer who would benefit from treatment with antibody-drug conjugates; and Apply evidence-based strategies to connect testing to treatment in patients with HER2-low or -ultralow advanced breast cancer.

Are you up to date on HER2 testing best practices? Join our expert panel and discover the critical updates that guide treatment selection. Credit available for this activity expires: 2/17/27 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/navigating-her2-spectrum-breast-cancer-evolving-diagnostic-2026a10004ea?ecd=bdc_podcast_libsyn_mscpedu

Drs. Dizon and Campos discuss how new antibody drug conjugates like trastuzumab deruxtecan are transforming treatment options for HER2+ gynecological cancers, showing promising results even in patients with low HER2 expression. They shared impressive clinical trial successes while emphasizing the importance of ongoing research into treatment sequencing and patient safety.

Breast cancer screening is often treated as a given. Mammograms are framed as routine, early detection as unquestionably life-saving, and following guidelines as the responsible choice. But what if the full picture is more complicated?In this episode of hol+, Dr. Taz sits down with integrative oncologist and breast surgeon Dr. Jenn Simmons, author of The Smart Woman's Guide to Breast Cancer, to explore what breast cancer screening data actually shows, where common narratives may oversimplify reality, and how statistics can sometimes be misunderstood by both patients and providers.Together, they discuss the difference between screening and diagnostic imaging, why detecting more cancers does not always mean fewer deaths, and how concepts like overdiagnosis and lead-time bias shape our interpretation of outcomes. Dr. Jenn also explains how breast cancer behaves differently from many other cancers, why progression is not always linear, and what tumor markers like ER, PR, HER2, and triple-negative really indicate.The conversation expands beyond imaging into a whole-body view of breast health, touching on inflammation, immune function, metabolic health, toxic burden, stress, and lifestyle as factors that shape cancer risk and recovery. Rather than promoting fear or urgency, this episode focuses on helping listeners understand their bodies, ask better questions, and make informed decisions with clarity.This episode is for anyone who wants a deeper understanding of breast cancer screening, feels overwhelmed by conflicting guidance, or wants to approach breast health with more nuance and less panic.About Dr. Jenn SimmonsDr. Jenn Simmons is an integrative oncologist, breast surgeon, and founder of Real Health MD. She was Philadelphia's first fellowship-trained breast surgeon and spent nearly two decades leading one of the region's top breast programs before transitioning into integrative oncology.Drawing from her experience in conventional cancer care and her own health journey, Dr. Simmons now focuses on whole-body approaches to breast health, cancer prevention, and recovery, including metabolic health, inflammation, immune function, lifestyle medicine, and root-cause healing. She is the author of The Smart Woman's Guide to Breast Cancer, a patient-centered resource designed to help women better understand their diagnosis, ask informed questions, and navigate treatment decisions with clarity rather than fear.Order the BookThe Smart Woman's Guide to Breast Cancer Stay Connected:Connect further to Hol+ at https://holplus.co/- Don't forget to like, subscribe, and hit the notification bell to stay updated on future episodes of hol+.Follow Dr. Jenn SimmonsInstagram: https://www.instagram.com/drjennsimmonsYouTube: https://www.youtube.com/@dr.jennsimmonsWebsite: https://www.jennsimmonsmd.com/Follow Dr. Taz on Instagram: https://www.instagram.com/drtazmd/https://www.instagram.com/liveholplus/Subscribe to the audio podcast: https://holplus.transistor.fm/subscribeSubscribe to the video podcast: https://www.youtube.com/@DrTazMD/podcastsGet your copy of The Hormone Shift: Balance Your Body and Thrive Through Midlife and MenopauseHost & Production TeamHost: Dr. Taz; Produced by ClipGrowth.com (Producer: Pat Gostek)00:00 Swedish trial claim and overdiagnosis framing 00:52 Why this became a part two conversation 03:25 Reframing screening narratives and medical training gaps 04:39 Why Dr. Simmons questions mammograms as a screening tool 06:06 Origins of screening programs and “invitation to screen” bias 07:12 Relative risk vs absolute numbers example (4 vs 5 per 1,000) 08:49 Overdiagnosis explained with a vivid analogy 09:50 Autopsy-study claim and the “microscopic cancer” idea 12:11 Swedish trial claim revisited: more diagnoses, same deaths 13:38 Downstream harms: callbacks, biopsies, overtreatment 15:04 Lead-time bias and survival statistics explained 16:44 Dr. Simmons' view on the founder's regret narrative 18:16 Switzerland headline clarified and what actually changed 20:10 Cautionary stories and aggressive cancers discussion 22:07 Why breast cancer does not always progress linearly 24:21 Buckets: DCIS, invasive, inflammatory, receptor types 26:15 Clinical vs subclinical disease approach 28:25 Long-term tradeoffs and “forgotten woman” after treatment 32:15 What ER PR HER2 mean biologically and system incentives 35:33 Testosterone discussion and prevention claim presented 42:15 Hormones after breast cancer and the 4-year “reintroduction” idea 44:29 Triple negative: environment, toxicity, immune system focus 49:19 What to do next: pause, exceptions, whole-body workup 52:32 Prevention and breast health approach begins 53:24 At-home tears test explanation (as discussed) 56:24 Detox basics and why sweating is emphasized 59:34 Imaging preferences for screening and what to do if limited access

Drs. Campos and Dizon explore how groundbreaking research is redefining HER2-targeted therapies in gynecological cancers, moving beyond the old one-size-fits-all approach. They spotlight the promise and ongoing challenges of customizing treatment using new biomarkers and clinical trial data.

Twenty years ago, seven people diagnosed with metastatic HER2-positive breast cancer received a cancer vaccine as part of a clinical trial. Today, they're all still alive. This prompted Zachary Hartman to study the immune systems of the people in the trial to see what was happening. He found that the women had immune cells that continue to recognize the cancer and keep it under control. Now his goal is to make that vaccine even more effective and make it work on other types of breast cancer. Listen to the episode to hear Dr. Hartman explain: how the original study was done how he's working to make the vaccine even more effective how the vaccine might be modified to work on hormone receptor-positive and triple-negative breast cancer

Cancer care is rapidly shifting toward precision medicine—treatment guided by a tumor's biology and biomarkers rather than where it starts in the body. HER2 is a protein on some cancer cells that can drive tumor growth. In this episode, we explore what it means for HER2 to be a target across multiple solid tumors, how […]

Cancer care is rapidly shifting toward precision medicine—treatment guided by a tumor's biology and biomarkers rather than where it starts in the body. HER2 is a protein on some cancer cells that can drive tumor growth. In this episode, we explore what it means for HER2 to be a target across multiple solid tumors, how […]

We love to hear from our listeners. Send us a message.In episode 122 of Cell & Gene: The Podcast, Host Erin Harris talks to Paul Romness, CEO of OS Therapies, to learn the company's mission to address the severe unmet need in pulmonary metastatic osteosarcoma (PMO), a rare pediatric cancer with no established standard of care once it metastasizes. Romness explains how OS Therapies' off-the-shelf HER2-targeted immunotherapy aims to significantly improve outcomes by stimulating a robust immune response with minimal side effects. He highlights results from a multicenter Phase 2B trial showing markedly improved overall survival rates compared to historical outcomes, details the company's constructive regulatory interactions with the FDA, and underscores the value of comparative canine biomarkers in development.Subscribe to the podcast!Apple | Spotify | YouTube Visit my website: Cell & Gene Connect with me on LinkedIn

In this episode of Denatured, Jennifer C. Smith-Parker speaks with Dr. Rob Monroe, Vice President and Chief Scientific Officer of Oncology at Danaher Corporation and Chief Medical Officer at Leica Biosystems, and Jennifer Fakish, Vice President and Franchise Head of Oncology at Danaher Corporation. We'll be discussing how antibody drug conjugates (ADCs) are transforming cancer care and with AI-powered pathology, doctors can now measure her HER2 more precisely to match patients with the best treatments. HostJennifer Smith-Parker, Director of Insights, BioSpaceGuestsDr. Rob Monroe, Vice President and Chief Scientific Officer, Oncology, Danaher Corporation; Chief Medical Officer, Leica BiosystemsJennifer Faikish, Vice President and Franchise Head, Oncology, Danaher CorporationDisclaimer: The views expressed in this discussion by guests are their own and do not represent those of their organizations.

In today's episode, our discussion features Aditya Bardia, MD, MPH, FASCO. Dr Bardia is a professor in the Department of Medicine in the Division of Hematology/Oncology, the director of Translational Research Integration, and a member of Signal Transduction and Therapeutics at the UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, California.In our exclusive interview, Dr Bardia discussed key findings from the phase 3 lidERA Breast Cancer study (NCT04961996) showing the invasive disease–free survival superiority of giredestrant (GDC-9545) over standard endocrine therapy in patients with estrogen receptor–positive, HER2-negative early breast cancer. Our discussion also covered the ongoing phase 3 INAVO123 trial (NCT06790693), which is investigating inavolisib (Itovebi) plus CDK4/6 inhibitors and letrozole in patients with endocrine-sensitive, PIK3CA-mutated breast cancer. Dr Bardia also emphasized the importance of testing for ESR1 and PIK3CA mutations in order to better personalize treatment.

In this episode of the Oncology Brothers podcast, we dived deep into the recent FDA approval of T-DXd (trastuzumab deruxtecan) plus Pertuzumab for the treatment of HER2-positive metastatic breast cancer. Joined by Dr. Sara Tolaney, the lead author of the DESTINY-Breast 09 study, where we discussed the findings that show a significant improvement in progression-free survival (PFS) from 26.9 months to 40.7 months, with a hazard ratio of 0.56. Key topics included: • The design and findings of the DESTINY-Breast09 trial • Comparison with traditional treatment regimen THP (trastuzumab, pertuzumab, and taxane) • The implications of these findings for clinical practice • The role of maintenance therapy and the potential for personalized treatment strategies • Common side effects associated with T-DXd and pertuzumab, including ILD (Interstitial Lung Disease) Join us as we explore the future of HER2-positive breast cancer treatment and the exciting developments that are changing the landscape for 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 subscribe for more insights on treatment algorithms, FDA approvals, and conference highlights! #HER2positiveBreastCancer, #TrastuzumabDeruxtecan, #DestinyBreast09, #MetastaticBreastCancer, #OncologyBrothers

Dr. Joshua Reuss is back on the podcast to discuss the full update to the living guideline on stage IV NSCLC without driver alterations. He discusses the new evidence and how this impacts the latest recommendations on first-line and subsequent therapeutic options. Dr. Reuss emphasizes the need for shared decision-making between clinicians and patients. He shares ongoing research that the panel will review in the future for further updates to this living guideline, and puts the updated recommendations into context for clinicians treating patients with stage IV NSCLC. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2026.3.0" at www.asco.org/thoracic-cancer-guidelines" TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology,  https://ascopubs.org/doi/10.1200/JCO-25-02825    Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Joshua Reuss from Georgetown University, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2026.3.0." It is great to have you back on the show today, Dr. Reuss. Dr. Joshua Reuss: Happy to be here, Brittany. Brittany Harvey: Just before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Reuss who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. Dr. Reuss, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer without driver alterations is updated on an ongoing basis. So, what prompted this latest update to the recommendations? Dr. Joshua Reuss: Our committee is tasked with making routine updates to the living guidelines and really keeping them living, right? So, evaluating new data as it is coming in to see, is this practice changing? Is this data that should inform and potentially alter our guideline recommendations so that practitioners and other care providers could really make the best treatment decisions for their patients? So that is something that happens on a more routine basis, but periodically, we are tasked with performing a more comprehensive update of our guideline where we really evaluate every one of our point recommendations, the data associated with these recommendations, to be sure that these are up to date, these are comprehensive, and to see if we need to alter anything in the language of these updates. Brittany Harvey: Excellent. Thank you for providing that background. And yes, this is truly a comprehensive update that goes through all the latest literature. Given that, I would like to review what has changed and what is new in the recommendations. So, what are the updated recommendations on first-line therapy for patients with stage IV non-small cell lung cancer without driver alterations? Dr. Joshua Reuss: So there are two main guidelines that we recommend from this panel. One is a driver mutation-positive guideline and the other is a driver mutation-negative guideline. And I think on first blush, one might look at kind of the recent flurry of approvals and new data and say, well, all the excitement, you know, is in the driver mutation-positive guideline. But I would say that the driver mutation-negative guideline is equally as important and really has several unique challenges associated with it. You know, first and foremost is that there are really a multitude of regimens that can be considered for any one patient. And how to choose between one can be quite difficult and a stressful challenge that clinicians can have, particularly since there are really no randomized studies comparing these regimens in a head-to-head fashion. In addition, you know, these guidelines are really broken down by two key factors. One is disease histology, so namely squamous versus non-squamous histology. And the other is PD-L1 status, broken down into one of three tertiles: PD-L1 high, which is greater than or equal to 50% expression; PD-L1 low, which is 1% to 49% expression; and then PD-L1 negative or unknown. So what you are really looking at, if you do that math, is really six unique patient subpopulations where we need to make a recommendation on one of the multitude of treatment regimens that is approved. And what that means is you are oftentimes really looking at subset and sub-subset level data to help inform clinicians in their treatment decision making, which can be quite challenging because as those small subsets of data is more and more parsed, there are many confounders that can be interjected there. And so I think the committee is tasked with really quite a challenge in terms of how to really communicate and broadcast that data in a way that informs clinicians in making a decision on what is the right treatment for their patient. Brittany Harvey: Absolutely. It can be challenging to interpret that subgroup data across several different studies that are reporting on different regimens and different outcomes. And I appreciate you mentioning the driver mutation-positive guideline as well. Listeners can check out the companion episode with Dr. Puri for more information on what is changed in the driver mutation-positive guideline. Based on that primer, what is new for first-line therapy for patients with stage IV non-small cell lung cancer without driver alterations? Dr. Joshua Reuss: Even though I will say there is not a lot of new trial data that was incorporated into this guideline, there were some updates and just some meaningful long-term data that we incorporated. I think first and foremost, there is a new top-level recommendation in this guideline pertaining to molecular testing, which is absolutely critical in both the driver mutation-positive and driver mutation-negative space. I think we tend to think that, oh, well, molecular testing really only pertains to then finding a driver mutation. But the lack of a mutation is absolutely critical as well, right? Because that is what leads us down the mutation-negative pathway. We also need this molecular testing to assess PD-L1 status. We are seeing emerging data on molecular mutations that might confer resistance to certain immunotherapy-based strategies. So the committee felt strongly that a recommendation on molecular testing is critical to include in both the driver mutation-positive guideline and the driver mutation-negative guideline. I will also say that we are now seeing five and six-year updates from some of the landmark trials of immunotherapy in driver mutation-negative non-small cell lung cancer. It is really incredible to see that in some of these trials, we are seeing very impressive durability of the treatment in the patient subsets that we are commenting on. In others, perhaps that durability is less clear, and I think that leads to challenges in making a recommendation on any one particular regimen. And I think that is nowhere more clear than in the squamous subset. I think that was one perhaps subtle change that is in this guideline where, particularly in the PD-L1 negative squamous population, the committee felt that no one regimen really was worthy of standing above the others. Sometimes I think it is important to really champion one unique regimen if we feel that the data is there to support it. But I think it is equally important to list multiple regimens where the data is less clear. I think another point is that while perhaps there were no new regimens that we have added or that led to other clear changes in the prioritization of one regimen over another, there are other unique data subsets that I think come into play in making a decision and that really are important when looking at the discussion on any one recommendation from this guideline. For example, we know there is emerging data on perhaps the significance of molecular alterations in KEAP1 or STK11 and how that might influence frontline decision-making. You know, there is not a prospective phase III trial in this population, but I think we still need to use that data in certain scenarios to make recommendations for a particular patient. Another example of a trial that, again, did not change our recommendations, but I think one can incorporate in their decision making is the KEYNOTE-598 trial. Now, this is not a new study, but what it studied was pembrolizumab versus pembrolizumab plus ipilimumab in a PD-L1 high subset, and found that the addition of ipilimumab to pembrolizumab in the PD-L1 high population did not significantly improve clinical efficacy. And so while pembrolizumab plus ipilimumab is not an approved regimen, it is hard to extrapolate that to our combination treatments that are approved. I think some clinicians might find that data valuable when making a frontline treatment decision on a patient who has PD-L1 high status. So a bit of a whirlwind tour, but I think there are still multiple factors that went into this guideline that are important to review when making treatment decisions for any one patient. Brittany Harvey: Absolutely. I think what you just mentioned in having that upfront molecular testing is really key for individualized patient care. And the evidence summaries that you provide in addition to the recommendations are really important for clinicians to be able to refer to as they are making decisions in their clinic. So then beyond those changes for first-line therapy, what is updated for second-line and subsequent therapies? Dr. Joshua Reuss: For second-line and subsequent therapies, we did see one new treatment recommendation join these ranks, and that was telisotuzumab vedotin. Telisotuzumab vedotin, quite a mouthful. That is an antibody-drug conjugate. I like to think of that as smart chemotherapy, targeted chemotherapy, where you are trying to utilize some aspect of a marker that is selectively expressed or overexpressed on the cancer surface to then shepherd in the anticancer molecule, a highly potent chemotherapeutic in the case of currently approved antibody-drug conjugates, to exert antitumor killing effect. So in this case, the antibody-drug conjugate telisotuzumab vedotin targets MET overexpression. So telisotuzumab is an antibody targeting MET, and that is conjugated to an MMAE highly potent chemotherapeutic payload called vedotin. So we know MET can be selectively expressed and overexpressed in non-small cell lung cancer in both driver mutation-positive and mutation-negative subsets. The data that led to this approval was from the phase II LUMINOSITY trial which evaluated telisotuzumab vedotin, or Teliso-V, in many subsets. But the subset that really showed promise and was expanded was the EGFR wild-type, non-squamous, non-small cell lung cancer population with MET overexpression. And so in 78 patients with high levels of expression, the response rate here was 34.6%, median progression-free survival of 5.5 months, and a median overall survival of 14.6 months. With an overall acceptable safety profile; grade 3 or higher adverse events, neuropathy was perhaps the most common at 7%, also increased ALT at 3.5%, and pneumonitis at 2.9%. Now this was phase II data that led to an accelerated approval. There is an ongoing phase III study randomizing patients with high expression to Teliso-V versus docetaxel. That is the phase III TeliMET study. But it is nice that we now have another option for patients, perhaps a more biomarker-directed option with, again, this MET overexpression. And again, it further reinforces the importance of molecular testing in patients with traditionally driver mutation-negative non-small cell lung cancer, whether that is upfront or at progression, and in particular utilizing immunohistochemistry to assess MET expression in these patients. And this does join another ADC that we had previously made an update in our recommendation, which is trastuzumab deruxtecan, which is approved for those patients with HER2-overexpressing non-small cell lung cancer. So just again to reiterate the importance of molecular testing in patients both at the outset of their treatment and upon progression on frontline therapy. Brittany Harvey: Definitely. It is great to have this new antibody-drug conjugate join the treatment options, and as you mentioned, very important in this case to have that molecular testing done at the outset and at progression. So then in your view, what should clinicians know as they implement this living guideline, and how do these changes impact patients with non-small cell lung cancer? Dr. Joshua Reuss: Because there are so many different regimens that one can consider for any one patient, I think it is easy to become overwhelmed and stress on, "Am I making the right choice for my patient?" And I think one of the key take home points is that in many cases, there is no one right regimen. And I think one has to weigh several factors. It is the treatment schedule. It is the toxicity profile. It is the molecular profile of the patient. It is the patient preference. You know, there are so many factors here. And I would like to draw the reader and viewer's attention to an important section of these guidelines, particularly the Patient and Clinician Communication section, where we have a box focused on discussion points between patients and clinicians, which I think focuses on several of the high-level points that one can emphasize in making these decisions, ranging on things from: what are the goals of the treatment? What are the risks and benefits to any one approach? What are comorbidities that should be factored in? Common concerns, toxicity management, clinical trial consideration. All of these factors that I think are incredibly important in making that frontline treatment decision and implementing a regimen that both the clinician and, more importantly, the patient feels comfortable with. Brittany Harvey: It is really important that there is shared decision-making in these scenarios. And I think that patient-clinician communication section can tease out some of those preferences from the patient end and talk through the risks and benefits of different regimens as well. As we mentioned at the top of this episode, this guideline is a living guideline and updated on an ongoing basis. So what is the panel examining and keeping an eye on for future updates to this guideline? Dr. Joshua Reuss: So I think there are a lot of exciting new therapies and more up-to-date trials that we are anxiously awaiting the results of on our committee, and I think the oncology community in general is awaiting the results of. When we will have these results, I think, is a bit of an open-ended question, but I can give some insight on several of the trials that our committee is really keeping a close eye on. One that we have mentioned for several guideline iterations is the ECOG-ACRIN INSIGNA trial. This is a phase III clinical trial comparing pembrolizumab versus pembrolizumab plus carboplatin and pemetrexed chemotherapy in PD-L1 positive, non-squamous, non-small cell lung cancer. We talk about there being different regimens that can be considered in PD-L1 positive and PD-L1 high subsets, namely immunotherapy alone or immunotherapy plus chemotherapy, but there is no direct head-to-head comparison here. So this trial hopefully will answer that question. It has now finished accrual. There are other very interesting molecules and trials. I think another interesting compound is ivonescimab. This is a PD-1/VEGF bispecific antibody that is currently approved in China as monotherapy in patients with PD-L1 positive non-small cell lung cancer based off of the HARMONi-2 trial, where the progression-free survival of this bispecific antibody, ivonescimab, appeared superior to pembrolizumab. And we are looking closely at ongoing trials to see if these results will be replicated in an ex-China population. And if so, I think it could have a real impact and change on our guidelines. Still other very interesting things. There are obviously confirmatory studies for antibody-drug conjugates, such as the TeliMET study that I alluded to earlier, and many promising antibody-drug conjugates, both bispecific and trispecific antibody-drug conjugates, that hopefully can inform practice. And then there are several unique subsets of populations that I think we now are utilizing data on to make decisions, but a lot of that is retrospective in small subsets where we do not have that prospective data. And there are several trials ongoing in some of these subsets to try to gain clarity on what regimen may be the best for patients. One example is the phase III TRITON trial, which is looking at comparing CTLA-4 containing regimen, particularly the POSEIDON regimen of durvalumab plus tremelimumab and chemotherapy, versus the KEYNOTE-189 regimen, which is pembrolizumab plus carboplatin and pemetrexed, in patients with non-squamous, non-small cell lung cancer that have alterations in either KRAS, KEAP1, and/or STK11. There is a lot of both preclinical and clinical data to suggest that patients with these alterations in STK11 and KEAP1 may be more resistant to a PD-1 based treatment approach, and perhaps the incorporation of CTLA-4 can lead to a more meaningful response in this unique subset. Obviously, that data, it is retrospective, it is in small subsets. And when you add in a CTLA-4 molecule, you are also introducing greater risk for toxicity. So this trial is going to be very important in elucidating: is there a benefit in that unique subset? Does that data that we see retrospectively in this small subset hold true when evaluated in a prospective fashion? So while our guideline, our most recent comprehensive panel update, may not have had a lot of new data in it that has influenced frontline treatment decision-making, I think the future is bright and there are a lot of novel studies and novel treatments on the horizon that will hopefully improve the outcomes for our patients. Brittany Harvey: Absolutely. We will look forward to the results of those ongoing trials to provide more options and particularly clarity for patients with non-small cell lung cancer and to inform this guideline and its many updates to come. So I want to thank you so much for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Reuss. Dr. Joshua Reuss: Thank you so much. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines App available in the Apple App Store or the Google Play Store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Dr. Sonam Puri discusses the full update to the living guideline on stage IV NSCLC with driver alterations. She shares a new overarching recommendation on biomarking testing and explains the new recommendations and the supporting evidence for first-line and subsequent therapies for patients with stage IV NSCLC and driver alterations including EGFR, MET, ROS1, and HER2. Dr. Puri talks about the importance of this guideline and rapidly evolving areas of research that will impact future updates. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.0" at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology,  https://ascopubs.org/doi/10.1200/JCO-25-02822    Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Sonam Puri from Moffitt Cancer Center, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO Living Guideline, Version 2026.3.0." It's great to have you here today, Dr. Puri. Dr. Sonam Puri: Thanks, Brittany. Brittany Harvey: And then just before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Puri, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content that we're here today to talk about, Dr. Puri, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer with driver alterations is updated on an ongoing basis. So, what data prompted this latest update to the recommendations? Dr. Sonam Puri: So Brittany, non-small cell lung cancer is one of the fastest-moving areas in oncology right now, particularly when it comes to targeted therapy for driver alterations. New data are emerging continuously from clinical trials, regulatory approvals, real-world experience, which is exactly why these are living guidelines. The goal is to rapidly integrate important advances as they happen, rather than waiting for years for a traditional update. Since the last full update of the ASCO Stage IV Non-small Cell Lung Cancer Guideline with Driver Alterations published in 2024, there have been seven new regulatory approvals and changes in first-line therapy for some driver alterations. [This version] of the "Stage IV Non-small Cell Lung Cancer Guidelines with Driver Alterations" represents a full update, which means that the panel reviewed and refreshed every applicable section of the guideline to reflect the most current evidence across therapies including sequencing and clinical decision-making. This is to ensure that clinicians have up-to-date practical guidelines that keep pace with how quickly the field is evolving. Brittany Harvey: Absolutely. As you mentioned, this is a very fast-moving space and this full update helps condense all of those versions that the panel reviewed before into one document, along with additional approvals and new trials that you reviewed during this time period. So then, the first aspect of the guideline is there's a new overarching recommendation on biomarker testing. Could you speak a little bit to that updated recommendation? Dr. Sonam Puri: Yeah, definitely. So the panel has discussed and provided recommendations on comprehensive biomarker testing and its importance in all patients diagnosed with non-small cell lung cancer. Ideally, biomarker testing should include a broad-based next-generation sequencing panel, rather than single-gene tests, along with immunohistochemistry for important markers such as PD-L1, HER2, and MET. These results really drive treatment decisions, both in frontline settings for all patients diagnosed with non-small cell lung cancer and in subsequent line settings for patients with non-small cell lung cancer harboring certain targetable alterations. Specifically in the frontline setting, it helps determine whether a patient should receive upfront targeted therapy or immunotherapy-based approach. We now have strong data that shows that complete molecular profiling results before starting first-line therapy is associated with better overall survival and actually more cost-effective care. Using both tissue and blood-based testing can improve likelihood of getting actionable results in a timely way, and we've also provided guidance on platforms that include RNA sequencing, which are specifically helpful for identifying gene fusions that might be otherwise missed with other platforms. On the flip side, outside of a truly resource-limited setting, single-gene PCR testing really should not be routine anymore. This is what the panel recommends. It's less sensitive and inefficient and increases the risk of missing important actionable alterations. Brittany Harvey: Understood. I appreciate you reviewing that recommendation. It really helps identify critical individual factors to match the best treatment option to each individual patient. So then, following that recommendation, what are the updated recommendations on first-line therapy for patients with stage IV non-small cell lung cancer with a driver alteration? Dr. Sonam Puri: Since the last full update in 2024, there have been four additional interim updates which were published across 2024 and 2025. Compared to the last version, there have been several updates which have been included in this full update. One of the most important shifts has been in first-line treatment of patients with non-small cell lung cancer harboring the classical, or what we call as typical, EGFR mutation. The current version of the recommendation is based on the updated survival data from the phase III FLAURA2 and MARIPOSA studies, based on which the panel recommended to offer either osimertinib combined with platinum-pemetrexed chemotherapy or the combination of amivantamab plus lazertinib in the first-line treatment of classical EGFR mutations. And these recommendations, as I mentioned, are grounded in the results of the FLAURA2 and MARIPOSA trials, both of which demonstrated improvement in progression-free survival and overall survival compared to osimertinib alone in patients with common EGFR mutations. That being said, the panel actually spent significant time discussing the toxicities associated with these treatments as well. These combination approaches come with higher toxicity, longer infusion time, increased treatment frequency. So while combination therapy is now recommended as preferred, the panel has recommended that osimertinib monotherapy remains a reasonable option, particularly for patients with poor performance status and for those who are not interested in treatment intensification after knowing the risks and benefits. Brittany Harvey: Absolutely. It's important to consider both those benefits and risks of those adverse events that you mentioned to match appropriately individualized patient care. So then, beyond those recommendations for first-line therapy, what is new for second-line and subsequent therapies? Dr. Sonam Puri: So this is a section that saw several major updates, particularly again in the EGFR space. The first was an update on treatment after progression on osimertinib for patients with classical EGFR mutation. Here the panel recommends the combination of amivantamab plus chemotherapy, and this recommendation was based on the phase III MARIPOSA-2 trial, which compared amivantamab plus chemotherapy with chemotherapy alone with progression-free survival as the primary endpoint. The study met its primary endpoint, showing an improvement in median PFS with the combination of amivantamab plus chemotherapy compared to chemotherapy alone. And as expected, the combination was associated with higher toxicity. So, although the panel recommends this regimen, the panel emphasizes that patients should be counseled on the side effects which may be moderate to severe with the combination therapy approach. In addition, a new recommendation was added for patients who are not candidates for amivantamab plus chemotherapy. In those cases, platinum-based chemotherapy with or without continuation of osimertinib may be offered, and the option of continuing osimertinib with chemotherapy was recommended and supported by data from a recently presented phase III COMPEL study, which randomized 98 patients with EGFR exon 19 deletion or L858R-mutated advanced non-small cell lung cancer who had experienced no CNS progression on first-line osimertinib, and these patients were randomized to receive platinum-pemetrexed chemotherapy with osimertinib or placebo. Although this study was small, it demonstrated a PFS benefit with continuation of osimertinib with chemotherapy, and this approach may be appropriate for patients without CNS progression who prefer or require alternatives to more intensive treatment strategies. Next was an update on options for patients with EGFR-mutated lung cancer after progression on osimertinib and platinum-based chemotherapy. Here the panel recommended that for patients whose disease has progressed after both osimertinib and platinum-based chemotherapy, a new drug known as datopotamab deruxtecan can be offered as a treatment option. And this treatment recommendation was based on evaluation of pooled data from the TROPION-Lung01 and TROPION-Lung05 study, in which in the pooled analysis about 114 patients with EGFR-mutant non-small cell lung cancer were treated with Dato-DXd, 57% of whom had received three or more prior lines of treatment, and what was observed was an overall response rate of 45% with a median duration of response of 6.5 months. So definitely promising results. Next, we focused on updates to subsequent therapy options for patients with another type of EGFR mutation known as EGFR exon 20 insertion mutations. In this section, the panel added sunvozertinib as a subsequent line option after progression on platinum-based chemotherapy with or without amivantamab. Sunvozertinib is an oral, irreversible, and selective EGFR tyrosine kinase inhibitor with efficacy demonstrated in the phase II WU-KONG6 study conducted in Chinese patient population. In this study, amongst 104 patients with platinum-pretreated EGFR exon 20 mutated non-small cell lung cancer, the observed response rate was 61%. Staying in the EGFR space, the panel added a recommendation for patients with acquired MET amplification following progression on EGFR TKI therapy. In these situations, the panel recommended that treatment may be offered with osimertinib in combination with either tepotinib or savolitinib. As our listeners may know, MET amplification occurs in approximately 10% to 15% of patients with EGFR-mutated non-small cell lung cancer when they progress on third-generation EGFR TKIs, and detection of MET amplification is done with various methods, such as tissue-based methods like FISH, NGS, and IHC, as well as ctDNA-based NGS with variable cut-offs. Over the last few years, several studies have informed this recommendation. I'm going to be discussing some of them. In the phase II ORCHARD trial, 32 patients with MET-amplified non-small cell lung cancer after progression on first-line osimertinib were evaluated, where the combination of osimertinib plus savolitinib achieved an overall response rate of 47% with a duration of response of 14.5 months. More recently, the phase II SAVANNAH trial reported outcomes in 80 patients with MET-amplified tumors after progression on osimertinib, and in this patient population, the combination of savolitinib and osimertinib achieved an overall response rate of 56% with a median PFS of 7.4 months. And lastly, the phase II single-arm INSIGHT 2 trial assessed the efficacy of osimertinib plus tepotinib in patients with advanced EGFR-mutant non-small cell lung cancer who had disease progression following first-line osimertinib therapy. And in this study, in a cohort of 98 patients with MET-amplified tumors confirmed by central testing, the overall response rate with the combination was 50% with a duration of response of 8.5 months. So definitely informing this guideline recommendation. Next, we had an update on recommendation in patients with ROS1-rearranged non-small cell lung cancer. For patients with ROS1-rearranged non-small cell lung cancer, the panel recommended specifically for patients who progressed after first-line ROS1 TKIs, the addition of taletrectinib as a new option alongside repotrectinib. And this recommendation was based on analysis of the results of the TRUST-I and TRUST-II studies, which showed that amongst 113 tyrosine kinase inhibitor-pretreated patients, taletrectinib achieved a confirmed overall response rate of 55.8% with a median duration of response of 16.6 months and a median PFS of 9.7 months, a very promising agent. Finally, for patients with HER2 exon 20 mutated non-small cell lung cancer, the panel added two new oral HER2 tyrosine kinase inhibitors, zongertinib and sevabertinib, as options in addition to T-DXd and after exposure to T-DXd. These recommendations are based on early phase data from two trials: the phase I Beamion LUNG-01 study, which evaluated zongertinib, and the phase I/II SOHO-01 study that evaluated sevabertinib. In this study, zongertinib demonstrated an overall response rate of 71% in previously treated patients, with an overall response rate of 48% amongst patients who had received prior HER2-directed ADCs including T-DXd. Sevabertinib in its early phase study showed an overall response rate of 64% in previously treated but HER2 therapy-naive patients, and an overall response rate of 38% in patients previously exposed to HER2-directed therapy. The panel believes that both agents had manageable toxicity profile and represent meaningful new options for this patient population. Brittany Harvey: Certainly, it's an active space of research, and I appreciate you reviewing the evidence underpinning all of these recommendations for our listeners. So, it's great to have these new options for patients in the later-line settings. And given all of these updates in both the first and the later-line settings, what should clinicians know as they implement this latest living guideline update, and how do these changes impact patients with non-small cell lung cancer? Dr. Sonam Puri: Some great questions, Brittany. I think for clinicians when implementing this update, I think about two practical steps. First is reiterating the importance of comprehensive biomarker testing. That is the only way to identify key drivers and resistance mechanisms that we are now targeting. And second, picking a first-line strategy that balances efficacy and toxicity and patient preference for your specific patient. I think informed decision-making, shared decision-making is more important than any time right now. It has always been important, but definitely very important now. For patients, this guideline brings recommendations on more personalized treatment options for both first-line and post-progression settings, which potentially means better outcomes. But it is also very important for our patients to continue to have informed conversations about side effects, time commitment, and what matters most to them with their providers. The panel in this version of the guideline specifically acknowledges the real-world barriers that prevent patients from receiving guideline-concordant therapy, including challenges with access to comprehensive molecular testing and treatment availability, and the panel emphasizes on the importance of shared decision-making, and we provide practical discussion points to help clinicians navigate these conversations with the patient. In addition, the panel has also addressed common real-world clinical complexities, such as treating elderly or frail patients, managing multiple chronic conditions, considerations around pregnancy and fertility, and certain disease scenarios such as oligoprogression or oligometastatic disease. And where available, the guideline summarizes this existing data to support informed individual decision-making in these complex situations. Brittany Harvey: Shared decision-making is really paramount, especially with all of the options and weighing the risks and benefits and considering the individual circumstances of each patient that comes before a clinician. We've talked a lot about all of the new studies that the panel has reviewed, but what other studies or areas of research is the panel examining for future updates to this living guideline as it continues to be updated on an ongoing basis? Dr. Sonam Puri: Yes, definitely, so much to look forward to, right? Looking ahead, the panel is closely monitoring several rapidly evolving areas that are likely to shape future updates of the guideline. This includes emerging data from ongoing later-phase studies, particularly the studies that are evaluating these new targeted agents moving to earlier lines of therapy, alongside studies evaluating additional combination strategies or more refined approaches to treatment sequencing. We're also closely watching advances in biomarker testing, the evolving understanding of resistance mechanisms, development of new targets, and promising therapeutic agents. I think ultimately the living guideline exists to help clinicians and patients navigate this rapidly evolving field, and we would like to ensure that scientific advances are rapidly translated into better, more personalized patient care. Brittany Harvey: Definitely. We'll look forward to those updates from those ongoing trials and future areas of research that you mentioned to provide better options for patients with non-small cell lung cancer and a driver alteration. So I want to thank you so much for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Puri. Dr. Sonam Puri: Thanks so much. Thanks so much for the opportunity. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. There's also a companion episode with Dr. Reuss on the related living guideline on stage IV non-small cell lung cancer without driver alterations that listeners can find in their feeds as well. And if you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

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

In today's episode, the discussion features Komal Jhaveri, MD, FACP, a breast medical oncologist at Memorial Sloan Kettering Cancer Center, who reviewed the evolving role of TROP2-directed antibody–drug conjugates (ADCs) in the management of hormone receptor (HR)–positive, HER2-negative metastatic breast cancer. She drew on findings from the phase 3 ASCENT-07 trial (NCT05840211), which evaluated sacituzumab govitecan-hziy (Trodelvy) in the first-line setting following endocrine therapy for patients with HR-positive, HER2-negative metastatic breast cancer.In this exclusive interview, Dr Jhaveri discussed the rationale for evaluating sacituzumab govitecan earlier in the treatment paradigm, summarized key efficacy outcomes from ASCENT-07, and contextualized why the trial did not meet its primary progression-free survival end point. She also highlighted how disease biology and patient selection may influence outcomes when ADCs are moved into earlier lines of therapy, and outlined practical considerations for toxicity management and future trial design as the TROP2 ADC landscape continues to evolve.asts, Spotify, and many of your other favorite podcast platforms,* so you get a notification every time a new episode is posted. While you are there, please take a moment to rate us!

Is the era of cisplatin over, or are we simply becoming more precise about who benefits from it? As perioperative strategies in bladder cancer continue to evolve, emerging tools like circulating tumor DNA (ctDNA) are playing a bigger role in how clinicians assess recurrence risk and tailor treatment. In this episode of BackTable Tumor Board, host Alan Tan, medical oncologist at Vanderbilt-Ingram Cancer Center, is joined by bladder cancer experts Dr. Amanda Nizam and Dr. Brad McGregor to discuss recent advances in the diagnosis and treatment of urothelial carcinoma. --- SYNPOSIS The doctors examine the evolving management of muscle-invasive bladder cancer (MIBC), including the role of neoadjuvant and adjuvant therapies, the integration of immunotherapy, and the recent approval of enfortumab vedotin plus pembrolizumab. The discussion explores the rapidly changing perioperative landscape, the prognostic utility of ctDNA, and how biomarkers such as HER2 and FGFR are influencing treatment selection across disease states. They also address bladder preservation strategies, management of treatment-related toxicities, and the importance of multidisciplinary coordination. The episode concludes with a forward-looking discussion on emerging therapies and the potential to improve cure rates in bladder cancer. --- TIMESTAMPS 00:00 - Introduction01:44 - Overview of Bladder Cancer Treatment04:54 - Patient Staging and Treatment Goals10:12 - Bladder Preservation vs. Radical Cystectomy16:39 - Emerging Trials and Future Directions22:40 - ctDNA and Precision Medicine33:50 - Metastatic Disease and Biomarker Strategies42:16 - Managing Neuropathy in Metastatic Treatment48:44 - HER2 and FGFR in Bladder Cancer54:15 - Future Directions in Bladder Cancer Treatment --- RESOURCES EV-302/303 Trialhttps://newsroom.astellas.com/2023-12-15-PADCEV-R-enfortumab-vedotin-ejfv-with-KEYTRUDA-R-pembrolizumab-Approved-by-FDA-as-the-First-and-Only-ADC-Plus-PD-1-to-Treat-Advanced-Bladder-Cancer NIAGARA Regimenhttps://www.nejm.org/doi/full/10.1056/NEJMoa2408154 KEYNOTE-905 Studyhttps://www.annalsofoncology.org/article/S0923-7534(25)04894-X/fulltext

In today's episode, the discussion features Aditya Bardia, MD, MPH, FASCO. Dr Bardia is a professor in the Department of Medicine in the Division of Hematology/Oncology, the director of Translational Research Integration, and a member of Signal Transduction and Therapeutics at the UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, California.In the exclusive interview, Dr Bardia discussed the rationale and design of the phase 3 ELEGANT study (NCT06492616), which is evaluating elacestrant (Orserdu) compared with standard endocrine therapy in patients with estrogen receptor–positive, HER2-negative early breast cancer at high risk of disease recurrence.

Did you know that as MBC patients get treated with multiple lines of ET, the percentage of patients who develop an ESR1 mutation increases? Credit available for this activity expires: 1/26/27 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/current-and-future-oral-serd-strategies-management-er-2026a100022b?ecd=bdc_podcast_libsyn_mscpedu

Featuring perspectives from Dr Haley Ellis, Prof Eric Van Cutsem and Dr Zev Wainberg, moderated by Dr Lionel A Kankeu Fonkoua, including the following topics:  Introduction (0:00) Biliary Tract Cancers — Dr Ellis (1:56) Gastroesophageal Cancers — Dr Wainberg (24:27) Colorectal Cancer — Prof Van Cutsem (59:13) CME information and select publications

Featuring perspectives from Dr Angela DeMichele, Dr Komal Jhaveri, Dr Erica Mayer, Dr Hope S Rugo and Dr Seth Wander, including the following topics:  Introduction (0:00) 1985 NCI Consensus Conference on Early Breast Cancer: Sir Richard Peto, FRS (2:01) Current Role of Genomic Assays in Treatment Decision-Making for Localized Hormone Receptor (HR)-Positive Breast Cancer — Dr DeMichele (5:13) Case: A premenopausal woman in her mid 40s with an ER-positive, HER2-negative, node-negative infiltrating ductal carcinoma (IDC) after partial mastectomy/radiation therapy who enrolls in the prospective, observational FLEX study: MammaPrint® low risk — Laurie Matt-Amaral, MD, MPH (15:30) Case: A premenopausal woman in her mid 40s after modified radical mastectomy for T2N0 ER-positive, HER2-negative IDC with an Oncotype DX® Recurrence Score (RS®) of 19 — Swati Vishwanathan, MD Case: A woman in her mid 60s with locally advanced (19 cm) ER-positive, HER2-low (IHC 1+) Stage IIIB mucinous carcinoma breast cancer and an RS of 18 — Alan B Astrow, MD (22:40) Role of CDK4/6 Inhibitors and Other Novel Strategies in Therapy for HR-Positive, HER2-Negative Localized Breast Cancer — Dr Jhaveri (30:18) Case: A woman in her mid 50s with ER-positive, HER2-negative Stage IIB, T2N1 IDC after neoadjuvant dose-dense AC-T, lumpectomy and adjuvant radiation therapy — Eleonora Teplinsky, MD (42:14) Case: A woman in her mid 60s with ER-positive, HER2-negative breast cancer with a surgically removed solitary lung metastasis after 4 years of adjuvant letrozole — Eric Fox, DO (46:32) Evolving Up-Front Treatment Paradigm for HR-Positive, HER2-Negative Metastatic Breast Cancer (mBC) — Dr Rugo (49:45) Case: A woman in her early 80s with Type 2 diabetes, well controlled hypertension and recurrent ER-positive, HER2-negative mBC after 4 years of adjuvant letrozole — Sunil Gandhi, MD (1:02:30) Clinical Utility of Agents Targeting the PI3K/AKT/mTOR Pathway for Patients with Progressive HR-Positive mBC — Dr Mayer (1:06:37) Case: A woman in her late 60s with ER-positive, HER2-low (IHC 1+), PIK3CA-mutant mBC with disease progression after 2 years of adjuvant letrozole — Laila Agrawal, MD (1:20:22) Case: A woman in her early 60s with ER-positive, HER2-low PIK3CA-mutant mBC and disease progression on first-line palbociclib/fulvestrant — Dr Teplinsky (1:26:36) Results from the Global Phase III lidERA Breast Cancer Trial of Giredestrant versus Standard Endocrine Therapy as Adjuvant Treatment for ER-Positive, HER2-Negative Localized Breast Cancer (1:31:48) Current and Future Role of Oral Selective Estrogen Receptor Degraders for Progressive HR-Positive mBC — Dr Wander (1:42:30) Case: A woman in her early 100s with locally advanced ER-positive, HER2-negative breast cancer with disease progression on letrozole, now with an ESR1 mutation — Dr Astrow (1:57:51) CME information and select publications

In this podcast, experts William J. Gradishar, MD, FASCO, FACP; Stephanie L. Graff, MD, FACP, FASCO; and Cynthia X. Ma, MD, PhD; discuss current and emerging therapeutic options, including next-generation endocrine therapies, to target the estrogen receptor signaling pathway for the treatment of hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (MBC).

Marybeth was diagnosed with stage 0 ER+, HER2+ breast cancer in 2007 at age 39, and 13 years later learned her cancer had metastasized to her bones and lymph system. At her therapist's suggestion, she read Radical Remission, which gave her hope, shifted her mindset, and showed her that healing beyond the statistics was possible. The book propelled her to explore peer-reviewed research and adopt powerful anti-cancer strategies. Within three months she achieved a complete pathological response, and she has now been cancer-free for more than five years. Outperform Cancer Website: www.outperformcancer.com Outperform Cancer Podcast on Apple and Spotify Facebook: https://www.facebook.com/outperformcancer Instagram: https://www.instagram.com/marybethgilliam Threads: https://www.threads.com/@marybethgilliam X: https://x.com/marybethgilliam Blue Sky: https://bsky.app/profile/outperformcancer.bsky.social Resources: American Association for Cancer Research (AACR)-https://www.aacr.org/ National Breast Cancer Coalition (NBCC)-https://www.stopbreastcancer.org/ ___________ To learn more about the 10 Radical Remission Healing Factors, connect with a certified RR coach or join a virtual or in-person workshop visit www.radicalremission.com.   To watch Episode 1 of the Radical Remission Docuseries for free, visit our YouTube channel here.  To purchase the full 10-episode Radical Remission Docuseries visit Hay House Online Learning. To learn more about Radical Remission health coaching with Liz or Karla, Click Here Follow us on Social Media: Facebook  Instagram YouTube _______________