Podcasts about pd l1

Play Episode Listen Later May 20, 2026 8:27

Featuring proceedings from a live event on January 9, 2026, held adjunct to the 2026 ASCO Gastrointestinal Cancers Symposium and moderated by Dr Samuel J Klempner, including the following topics: Treatment approach for metastatic HER2-negative, claudin 18.2-positive, microsatellite instability-high gastroesophageal (GE) cancer (0:00) Duration of chemotherapy for patients with advanced GE cancers receiving nivolumab/chemotherapy (3:06) Younger patient with metastatic PD-L1-positive gastric cancer (5:29) CME information and select publications

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Immune Checkpoint Inhibitors May Improve Outcomes in High-Risk Solid Tumors

Oncotarget

Play Episode Listen Later May 20, 2026 4:13

Cancer immunotherapy has transformed the treatment landscape for many advanced cancers over the past decade. Drugs targeting the PD-1 and PD-L1 pathways are now widely used across several tumor types, helping the immune system recognize and attack cancer cells more effectively. However, researchers are still working to understand how beneficial these therapies may be when used earlier in the disease course, particularly after surgery in patients with high-risk solid tumors. A research paper on this topic was published in Volume 17 of Oncotarget titled “Efficacy and safety of PD-1/ PD-L1 inhibitors as adjuvants in the treatment of patients with solid cancers: A systematic review and meta-analysis of randomized controlled trials.” Full blog - https://www.oncotarget.org/2026/05/20/immune-checkpoint-inhibitors-may-improve-outcomes-in-high-risk-solid-tumors/ Paper DOI - https://doi.org/10.18632/oncotarget.28855 Correspondence to - Dhai Almuteri - d.almuteri@qu.edu.sa Abstract video - https://www.youtube.com/watch?v=4Ce07bHfjB4 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28855 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, PD-1, PD-L1, adjuvant immunotherapy, solid tumor To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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Treating BRAF V600E Mutated Non-Small Cell Lung Cancer (NSCLC) with Dr. Gregory Riely

Play Episode Listen Later May 18, 2026 18:57

Welcome to the Oncology Brothers podcast! In this episode, we dived deep into the world of BRAF V600E-driven non-small cell lung cancer (NSCLC) with our guest Dr. Gregory Riely, a thoracic medical oncologist from Memorial Sloan Kettering Cancer Center. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Apple Podcast: https://podcasts.apple.com/us/podcast/oncology-brothers-practice-changing-cancer-discussions/id1653340966 Follow us on social media: ⁠X/Twitter: https://twitter.com/oncbrothers ⁠Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ Join us as we explore: The prevalence of BRAF V600E mutations in NSCLC and how they compare to other oncogenic drivers. The latest treatment options, including BRAF-MEK inhibitors like Encorafenib-Binimetinib and Dabrafenib-Trametinib. Key clinical trial data that led to the approval of these therapies and their implications for patient care. The role of immunotherapy in treating BRAF V600E patients and how to effectively sequence treatments. Patient characteristics that influence treatment decisions, including smoking history and PD-L1 expression. Whether you're a practicing oncologist or simply interested in the latest advancements in cancer treatment, this episode is packed with valuable insights and expert opinions. Don't miss it! Subscribe to our channel for more discussions on oncology and stay updated on the latest in cancer care! #BRAFV600E, #NSCLC, #BRAFMEKinhibitor, #TargetedTherapy, #OncologyBrothers

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237: Why Pathology Vendor's Don't Speak the Same Language?

Play Episode Listen Later May 18, 2026 33:08 Transcription Available

Send us Fan MailWhy are pathology vendors still speaking different image languages when radiology solved that problem decades ago?In this episode of DigiPath Digest #46, I talk through four papers that all point to a bigger issue in digital pathology: we are not only dealing with better algorithms. We are dealing with interoperability, workflow design, explainability, and whether the field is actually ready to use these tools well.I start with DICOM in digital pathology, because I think this is still one of the most important infrastructure questions in the field. Digital pathology has clear value for consultation, image analysis, archival, and workflow, but vendor-specific whole slide image formats still create silos. In the episode, I explain why DICOM matters, why adoption is still low, how the multi-resolution pyramid works, and why this is really about enterprise imaging and future-proofing, not just file conversion. Then I move into kidney transplant rejection, where the paper makes a strong case for multimodal precision diagnostics. Creatinine is late. Antibody testing can miss important biology. Biopsies can miss the area that matters. So the opportunity is not to replace pathology, but to combine biomarkers, biopsy, and machine learning in a way that is more useful than any one signal alone. I also talk about explainability here, because if a model gives a risk score, we need to know what contributed to it. The third paper focuses on perineural invasion in solid tumors, and I liked this one a lot because it shows how AI can help standardize something that is clinically important but still inconsistently detected and reported. Perineural invasion is not just a passive pathway of spread. The biology is more active than that, and the quantification can go far beyond a simple yes-or-no answer. This is a good example of where digital pathology can do something humans cannot realistically do by eye at scale. The last paper is on gastric cancer immunohistochemistry biomarkers and advanced quantification, including HER2, PD-L1, mismatch repair, and CLDN18.2. This section is really about complexity. We are now asking pathologists to visually score biology that is getting harder and harder to summarize consistently, especially when markers, spatial context, and multiplexing all start to matter at once. I make the case that computational pathology is becoming necessary here, not because pathologists are failing, but because the biology is outgrowing purely visual workflows. What ties these four papers together is simple: digital pathology is not only about remote reading anymore. It is about interoperability, quantification, explainable AI, and making pathology more precise in places where the old workflow is reaching its limit. If you are a pathologist, lab leader, or digital pathology trailblazer trying to figure out what actually matters right now, this episode will help you connect the dots.Episode Highlights 07:41 – Why DICOM still matters if we want digital pathology systems to work together. 14:39 – Current adoption of SVS, MRXS, and DICOM, and why DICOM is still lagging. 16:44 – How the DICOM whole slide image pyramid works and why it matters for workflow. 24:29 – Why kidney transplant rejection is still difficult to diagnose with any single marker. 29:18 – Why perineural invasion is clinically important and still inconsistently reported. 34:44 – How AI can quantify tumor-nerve relationships more consistently than visual review alone. 46:39 – Why gastric cancer biomarker scoring is getting too complex for purely visual workflows. 54:55 – Multiplexing, spatial biology, and why explainable AI matters in biomarker interpretation. 01:04:01 – What is really blocking digital pathology adoption: cost, workflow, regulation, or mindset? Resources mentionedDICOM / digital pathology interoperability paper https://pubmed.ncbi.nlm.nih.gov/42093730/Kidney transplant rejection, biomarkers, and artificial intelligence https://pubmed.ncbi.nlm.nih.gov/42073482/Perineural invasion in solid tumors with AI and machine learning applications https://pubmed.ncbi.nlm.nih.gov/42100436/Gastric cancer IHC biomarkers, advanced detection methods, and perspectives https://pubmed.ncbi.nlm.nih.gov/42075555/Digital Pathology Place https://digitalpathologyplace.comDigital Pathology 101 Free PDF book mentioned at the end of the episode through Digital Pathology Place.Support the showGet the "Digital Pathology 101" FREE E-book and join us!

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How to Treat Metastatic NSCLC W/O Targeted Mutations – Treatment Algorithm with Dr. Christine Garcia

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Play Episode Listen Later May 7, 2026 23:04

Welcome to the Oncology Brothers podcast! In this episode, we dived deep into the treatment algorithm for metastatic non-small cell lung cancer (NSCLC) without actionable driver mutations in frontline settings. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Apple Podcast: https://podcasts.apple.com/us/podcast/oncology-brothers-practice-changing-cancer-discussions/id1653340966 Follow us on social media: ⁠X/Twitter: https://twitter.com/oncbrothers ⁠Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ We discussed the latest updates in lung cancer treatment, including the recent approval of Teliso-V for C-MET overexpressing disease and Zongertinib for HER2 positive cases. We explored the nuances of choosing between single-agent and dual checkpoint inhibitors, the role of PD-L1 scores, and the impact of molecular testing on treatment decisions. Special guest Dr. Christine Garcia, a thoracic medical oncologist and fellowship program director at Weill Cornell Medicine, shared her insights on the importance of biomarker testing, the implications of STK11 and KEAP1 mutations, and the evolving landscape of KRAS inhibitors. Key topics covered in this episode: The significance of NGS testing and PD-L1 scores in treatment decisions The role of chemotherapy in high PD-L1 patients Insights on dual checkpoint inhibitors based on recent clinical trials The latest options for KRAS G12C mutations and C-MET overexpression Practical considerations for managing treatment-related side effects Tune in for an informative discussion that bridges the gap between academic research and community practice in oncology. Don't forget to subscribe for more episodes on treatment algorithms and the latest in cancer care! #MetastaticNSCLC, #Immunotherapy, #KRASG12C, #BiomarkerTesting, #OncologyBrothers

EVA CAST #40 - Cancer de ovário reistente ou refratário à platina, novas perspectivas

EVA CAST - o podcast do Grupo Brasileiro de Tumores GinecolÃ³gicos

Play Episode Listen Later May 5, 2026 45:13

O episódio 40 do EVA CAST, o podcast do Grupo Brasileiro de Tumores Ginecológicos, aborda o câncer de ovário resistente ou refratário à quimioterapia baseada em platina, um dos cenários mais desafiadores da Oncologia ginecológica. Em um contexto de alta incidência e mortalidade no Brasil, o episódio discute por que muitas pacientes ainda são diagnosticadas em estágios avançados e como isso contribui para recorrência frequente e limitação das respostas terapêuticas. Participam da conversa Alexssandra Lima, oncologista clínica do Grupo Oncoclínicas e pesquisadora do INCA; Lygia Soares, oncologista clínica e professora da UFRN; e Maria Eduarda Meyer, oncologista clínica do Centro Especializado em Oncologia de Florianópolis. As especialistas exploram a heterogeneidade do câncer de ovário, os fatores associados à recorrência e os critérios que definem sensibilidade ou resistência à platina, fundamentais para a organização do tratamento. O episódio detalha os mecanismos biológicos de resistência, como alterações no reparo do DNA e evasão da morte celular, além de discutir como esses processos impactam terapias subsequentes, incluindo os inibidores de PARP. Também apresenta avanços recentes, como terapias-alvo, imunoterapia e o uso de biomarcadores — BRCA, HRD, PD-L1, HER2 e receptor de folato alfa — na personalização do tratamento. A discussão inclui ainda os desafios do manejo clínico em múltiplas linhas de tratamento, o equilíbrio entre eficácia e qualidade de vida e as barreiras estruturais no Brasil, como desigualdade de acesso a diagnóstico, cirurgia especializada e terapias inovadoras. Como mensagem final, o episódio destaca que, apesar das limitações, a medicina de precisão abre caminho para melhores desfechos e maior individualização do cuidado.

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How to Treat Localized Non-Small Cell Lung cancer – Treatment Algorithm with Dr. Sanjay Popat

Play Episode Listen Later May 4, 2026 25:40

Welcome to another episode of the Oncology Brothers podcast! In this episode, hosts Rahul and Rohit Gosain dive deep into the treatment algorithms for early-stage non-small cell lung cancer (NSCLC) with curative intent. Joined by leading thoracic medical oncologist Dr. Sanjay Popat from London, they discussed the critical role of next-generation sequencing (NGS) in treatment planning, the importance of proper staging, and the implications of actionable mutations. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Apple Podcast: https://podcasts.apple.com/us/podcast/oncology-brothers-practice-changing-cancer-discussions/id1653340966 Follow us on social media: X/Twitter: https://twitter.com/oncbrothers ⁠Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ Key topics covered included: The significance of NGS testing and its impact on treatment decisions. Insights from the CHECKMATE 816 trial, highlighting the benefits of neoadjuvant chemoimmunotherapy. The complexities of post-operative immunotherapy and patient-shared decision-making. The role of adjuvant chemotherapy in patients with actionable mutations like EGFR and ALK. The latest data on osimertinib and alectinib in the adjuvant setting. The standard of care for unresectable disease based on the PACIFIC trial and the implications of PD-L1 status. Join us for an informative discussion that unpacks the latest advancements in NSCLC treatment and emphasizes the importance of personalized care. Don't forget to subscribe for more episodes in our treatment algorithm series! #EarlyStageNSCLC, #CHECKMATE816, #NeoadjuvantTherapy, #PrecisionMedicine, #OncologyBrothers

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S17 Ep12: ADCs Change Treatment Paradigms and Challenge Standard AE Management Protocols in TNBC: With Sara Nunnery, MD, MSCI; and Irene Morae Kang, MD

Play Episode Listen Later Apr 30, 2026 47:23

Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.In part 2 of this conversation, filmed live onsite at the 43rd Annual Miami Breast Cancer Conference, Dr Nunnery sat down with Irene Morae Kang, MD, an assistant professor in the Department of Medical Oncology & Therapeutics Research and the medical director of Women's Health Medical Oncology at City of Hope Orange County in Irvine, California.Their discussion focuses on the rapidly evolving treatment paradigm for first-line metastatic triple-negative breast cancer (TNBC), including the emergence of new data that is shifting standards of care. Dr Kang explained that TNBC is defined by the absence of estrogen, progesterone, and HER2 receptors, which historically restricted treatment options to non-targeted chemotherapy. A primary focus of the conversation was the role of PD-L1 expression and the use of immunotherapy. Dr Kang described PD-L1 as a checkpoint inhibitor protein on cancer cells that shuts off the immune system. By blocking this protein, oncologists can keep the body's T-cells vigilant to fight the cancer. However, she noted that immunotherapy is typically reserved for the approximately 40% of patients who express PD-L1 and may be contraindicated for those with active autoimmune diseases or a history of severe immune-related toxicities.The dialogue transitioned into the use of antibody-drug conjugates (ADCs). Dr Kang reviewed data from major trials using TROP2-targeting ADCs in the first-line setting. Dr Kang emphasized the importance of using these highly effective agents early, as many patients with TNBC do not survive to receive a second line of therapy.Finally, Dr Kang highlighted the distinct toxicity profiles and administration schedules that guide clinical decision-making. Although sacituzumab govitecan-hziy (Trodelvy) is frequently associated with neutropenia and alopecia, the primary toxicities associated with datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) are stomatitis and ocular adverse effects like dry eye. Using Dato-DXd in practice requires a rigorous prophylactic regimen, including steroid mouthwash and lubricating eye drops. Ultimately, Dr Kang noted that because efficacy appears similar between the 2 ADCs, the choice often rests on the patient's lifestyle, their ability to adhere to preventative AE protocols, and infusion schedule preference.

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Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancers — Microlearning Activity 3: Proceedings from a Session Held Adjunct to the 2026 ASCO GI Cancers Symposium

Play Episode Listen Later Apr 25, 2026 16:55

Featuring perspectives from Dr Jaffer A Ajani, Dr Samuel J Klempner, Dr Rutika Mehta and Dr John Strickler, moderated by Dr Klempner, including the following topics: Role of PD-L1 status, tumor histology and pulmonary disease in selection of immune checkpoint inhibition as up-front therapy (0:00) Impact of metastatic site and autoimmune disease on clinical decision-making in the use of immune checkpoint inhibition (5:56) Biomarker assessment approach and treatment selection (10:50) CME information and select publications

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Treating Advanced Skin Cancer Without Surgery: Hedgehog & PD-1 Inhibitors with Dr. Todd Schlesinger

Skincare Confidential

Play Episode Listen Later Apr 21, 2026 31:43

In this clinically rich episode, host Dr. Ted Lain sits down with board-certified dermatologist and global skin cancer expert Dr. Todd Schlesinger — AAD Board of Directors member, Mohs surgeon, clinical assistant professor at George Washington University School of Medicine, and medical director of the Clinical Research Center of the Carolinas — for a deep dive into systemic and targeted therapies for non-melanoma skin cancer (NMSC). The doctors begin with a thorough breakdown of the hedgehog signaling pathway (PATCHED, Smoothened, GLI-1 transcription) and how mutations in this pathway drive basal cell carcinoma (BCC) growth. They compare the two FDA-approved hedgehog pathway inhibitors (HHIs) — vismodegib (Erivedge) and sonidegib (Odomzo) — covering their mechanisms of action, volume of distribution differences (16–18L vs. ~9,000L), indications for locally advanced and metastatic BCC, how to define "locally advanced," and complete vs. partial response rates. Dosing strategies are addressed in detail, including alternate-day dosing and treatment breaks backed by the MIKIE study and STEVIE safety study. For managing the most common adverse events — muscle cramps, dysgeusia, weight loss, and fatigue — Dr. Schlesinger shares his clinical protocol using L-carnitine supplementation (1,500–2,000mg liquid, started 2–4 weeks before therapy) along with calcium and CoQ10. The conversation then moves to PD-1 and PD-L1 checkpoint inhibitors for locally advanced and metastatic cutaneous squamous cell carcinoma (cSCC) and BCC, covering cemiplimab (Libtayo), pembrolizumab (Keytruda), and nivolumab (Opdivo). The hosts explain the immune checkpoint mechanism using a memorable analogy, discuss how UV exposure upregulates PD-1 on tumor cells, and explore the practical realities of dermatologists prescribing infusion-based immunotherapy — including multidisciplinary care team logistics, buy-and-bill considerations, and when to partner with oncology. The episode closes with an exciting look at the pipeline: intralesional therapies for nodular and superficial BCC from companies including Verica, iViva, PHIO, and Feldan, red light PDT for superficial BCC nearing FDA approval, and the broader question of where these drugs fit as neoadjuvant, adjuvant, or primary therapies — and what complete response benchmarks (80–95%) dermatologists should expect before adopting non-surgical primary options. To watch this and other episodes, be sure to check out our YouTube page DISCLAIMER: This podcast is not intended to provide diagnosis, treatment, or medical advice. Content provided in this podcast is for educational purposes only. Please consult with a physician regarding any health-related diagnosis or treatment.See omnystudio.com/listener for privacy information.

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Myocardial Expression of PD-L1 as a Marker of Poor Prognosis in Immune Checkpoint Inhibitor–Associated Myocarditis | JACC: CardioOncology

JACC Speciality Journals

Play Episode Listen Later Apr 21, 2026 2:06

Research fellow, Adrian Chen, discusses a multicenter study evaluating myocardial PD‑L1 expression as a prognostic biomarker in immune checkpoint inhibitor–associated myocarditis. The conversation highlights how elevated myocardial PD‑L1 identifies patients at markedly higher risk for early adverse cardiac events and explores its potential role in improving risk stratification and guiding earlier, more aggressive therapy in this high‑risk population.

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229: Spatial Omics and AI for Clinically Actionable Cancer Biomarkers

Play Episode Listen Later Apr 20, 2026 22:37 Transcription Available

Send us Fan MailPaper Discussed in this Episode:Spatial omics and AI for clinically actionable cancer biomarkers. Reitsam NG. PLoS Med 2026; 23(4): e1005049.Episode Summary: In this deep dive, we explore how artificial intelligence and spatial omics are fundamentally rewriting the rules of cancer diagnostics. We break down a 2026 editorial that challenges a deceptively simple question driving modern oncology: Is a tumor "positive" or "negative" for a biomarker? As targeted cancer therapies evolve, this binary thinking is failing us. We discuss why mapping where and how much of a therapeutic target exists is crucial, and how AI is stepping in to solve the reproducibility issues human pathologists face when making borderline diagnostic calls.In This Episode, We Cover:• The Illusion of "Positive" vs. "Negative": Why the basic premise of modern cancer therapies—like antibody-drug conjugates (ADCs)—often falls apart in reality when we ignore the spatial heterogeneity of a tumor.• The Power of Computational Pathology: How AI is transforming subjective, qualitative estimates into continuous, reproducible data, scaling the quantification of complex biomarkers like PD-L1 and TROP2.• "Virtual" Proteomics: The fascinating concept of using AI models to infer high-dimensional spatial information and immune maps directly from standard, routine H&E stained slides.• The HER2 Bottleneck: A real-world look at the breast cancer drug T-DXd, which now demands pathologists distinguish between "HER2-low" and "HER2-ultralow". While human agreement drops below 70% at these fuzzy decision boundaries, AI steps up with a staggering ~97% sensitivity.• Three Shifts for the Future: Why clinical trials and routines must adopt continuous measures (like percentage of expressing cells), demand longitudinal repeat testing at disease progression, and utilize adaptive trial platforms.• Bridging the Gap to Reality: The massive hurdles preventing widespread adoption—such as equipment costs exceeding $250,000 and massive data storage needs. We discuss why a hybrid workflow that bolsters routine pathology with deployable AI is the best path forward to prevent widening global health disparities.Key Takeaway: The future of precision oncology isn't just about finding new drug targets; it's about fundamentally changing how we measure them. By moving away from rigid binary thresholds and using AI to map the continuous, spatial reality of tumors, we can unlock the true potential of targeted therapies. However, achieving this diagnostic ecosystem requires overcoming significant financial and systemic hurdles—such as updating reimbursement pathways and proficiency testing—to ensure these life-saving insights are accessible across all healthcare settings.Support the showGet the "Digital Pathology 101" FREE E-book and join us!

Lung Cancer — 5-Minute Journal Club with Dr Natalie Vokes: Current and Future Role of Tumor-Informed Circulating Tumor DNA Assays

Play Episode Listen Later Apr 17, 2026 27:12

Featuring an interview with Dr Natalie Vokes, including the following topics: Perioperative minimal residual disease (MRD) detected by circulating tumor DNA (ctDNA) testing in patients with lung cancer (0:00) Ohara S et al. Clinical significance of perioperative MRD detected by ctDNA in patients with lung cancer with a long follow-up data: An exploratory study. JTO Clin Res Rep 2024;6(3):100762. Abstract Masuda K et al. MRDSEEKER (JCOG2111A): A prospective study to evaluate MRD and its association with prognosis in curative-intent NSCLC. World Conference on Lung Cancer 2025;Abstract P3.18.04. Zhou C et al. IMpower010: Biomarkers of disease-free survival in a phase 3 study of atezolizumab vs best supportive care after adjuvant chemotherapy in stage IB-IIIA NSCLC. ESMO IO 2021;Abstract 2O. MRD analysis of adjuvant therapy with osimertinib for resected EGFR-mutated Stage IB to IIIA non-small cell lung cancer (NSCLC) (8:28) Herbst RS et al. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer. Nat Med 2025;31(6):1958-68. Abstract MRD analyses of perioperative chemoimmunotherapy for resected NSCLC (15:12) Forde PM et al. Overall survival with neoadjuvant nivolumab plus chemotherapy in lung cancer. N Engl J Med 2025;393(8):741-52. Abstract ctDNA dynamics in advanced NSCLC treated with immunotherapy (20:56) Vokes NI et al. Circulating tumor DNA (ctDNA) dynamics and survival outcomes in patients (pts) with advanced non-small cell lung cancer (aNSCLC) and high (>50%) programmed cell death ligand 1 (PD-L1) expression, randomized to cemiplimab (cemi) vs chemotherapy (chemo). ASCO 2023;Abstract 9022. Anagnostou V et al. ctDNA response after pembrolizumab in non-small cell lung cancer: Phase 2 adaptive trial results. Nat Med 2023;29(10):2559-69. Abstract Anagnostou V et al. A biomarker-directed, multi-center phase II/III study of ctDNA molecular response adaptive immuno-chemotherapy in patients with non-small cell lung cancer (BR.36). ASCO 2025;Abstract TPS8669. CME information and select publications

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S16 Ep52: Medical Crossfire®: PD-L1 Inhibition in Advanced Cutaneous Squamous Cell Carcinoma — Mechanistic Rationale and Clinical Application

Dr. Baliga's Internal Medicine Podcasts

Play Episode Listen Later Apr 15, 2026 31:27

In this podcast, experts April K.S. Salama, MD; Omid Hamid, MD; James M.G. Larkin, MD, PhD; and Sapna Patel, MD; discuss the data for immune checkpoint inhibitors used to treat advanced cutaneous squamous cell carcinoma, including a review of PD-1 versus PD-L1 inhibition.

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Reversing Heart Failure: Where immunology meets cardiology

Play Episode Listen Later Apr 12, 2026 4:05

A fascinating step forward in Nature—where immunology meets cardiology.

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224: AI and Computational Pathology in Breast Cancer Care

Play Episode Listen Later Apr 10, 2026 24:31 Transcription Available

Send us Fan MailPaper Discussed in this Episode: How artificial intelligence applied to digital pathology could guide treatment personalization in breast cancer. T. Ruelle, T. Grinda, L. Del Mastro, M. Lacroix-Triki, B. Pistilli & G. Gessain. ESMO Real World Data and Digital Oncology 2026.Episode Summary: In this journal club episode, we step into the reality of computational pathology and explore how artificial intelligence is fundamentally transforming breast cancer diagnostics. We examine a comprehensive review detailing how AI not only assists overburdened healthcare systems but also unlocks invisible genomic data straight from a standard $5 hematoxylin-eosin (H&E) glass slide. What happens when a machine can predict complex DNA mutations just by evaluating the structural architecture of cells?In This Episode, We Cover:• The Diagnostic Bottleneck: Understanding the critical worldwide shortage of pathologists colliding with a projected 3.2 million global breast cancer diagnoses by 2050, and why the system is under unprecedented strain.• The Biomarker Battle: Why the human visual cortex struggles to quantify faint immunohistochemistry stains, and how AI acts as a perfect "digital colorimeter". We discuss its near-perfect concordance in assessing crucial biomarkers like Ki-67, ER, PR, PD-L1, and the newly established HER2-low status.• Seeing the Invisible (Predictive AI): How deep learning transcends visual diagnostics to predict treatment outcomes, such as a patient's response to neoadjuvant chemotherapy. We also discuss AI's ability to infer Homologous Recombination Deficiency (HRD) and BRCA1/2 mutations by identifying macroscopic footprints like laminated fibrosis.• Decoding Genomic Assays: The potential to replace expensive, tissue-consuming genomic tests like Oncotype DX with AI models (such as Orpheus) that predict recurrence risk straight from digitized slides, achieving accuracy that rivals the tests themselves.• Roadblocks to Reality: The major clinical friction preventing global rollout. We discuss the steep infrastructure costs of whole-slide scanners, the danger of AI bias across diverse hospital datasets, and the ethical "black box" problem requiring the evolution of transparent, agent-based AI.Key Takeaway: Computational pathology is moving far beyond basic diagnostic assistance. By successfully reading the structural language of biology, AI proves it can extract costly, invisible molecular data from standard biopsies, fundamentally changing the economics and accessibility of global personalized healthcareSupport the showGet the "Digital Pathology 101" FREE E-book and join us!

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New Frontiers in Esophagogastric Cancer with Dr. Yelena Janjigian

Oncology Data Advisor

Play Episode Listen Later Apr 8, 2026 8:14

The treatment of esophagogastric cancer is undergoing a profound transformation. In this episode, Yelena Janjigian, MD (MSKCC), discusses how perioperative chemoimmunotherapy and precision biomarkers are redefining the standard of care. Key highlights include: - The Perioperative Shift: Why starting immunotherapy before surgery is achieving unprecedented pathologic responses. - Precision Testing: The essential role of MSI, PD-L1, HER2, and CLDN18.2 testing for every patient. - Avoiding Understaging: Why clinical evaluation must go beyond imaging to prevent missed therapeutic opportunities. - Multidisciplinary Success: The critical need for surgeon-oncologist communication before the first incision. Tune in to learn why "cure" is the new benchmark in localized disease and how to integrate these advances into your clinical practice today. Interested in the complete CE activity? Complete Module 1: https://bit.ly/45u106o Complete Module 2: https://bit.ly/3HtOziO

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Adjuvant PD-1/PD-L1 Inhibitors Show Efficacy but Highlight Safety Considerations in Solid Cancers

Oncotarget

Play Episode Listen Later Apr 7, 2026 2:49

BUFFALO, NY – April 7, 2026 – A new #research paper was #published in Volume 17 of Oncotarget on March 31, 2026, titled “Efficacy and safety of PD-1/ PD-L1 inhibitors as adjuvants in the treatment of patients with solid cancers: A systematic review and meta-analysis of randomized controlled trials.” Led by first author Maryam Aleid from Imam Abdulrahman Bin Faisal University, and corresponding author Dhai Almuteri from King Fahad Specialist Hospital, the researchers evaluated 13 randomized controlled trials involving 9,850 patients to assess the efficacy and safety of PD-1 and PD-L1 inhibitors as adjuvant therapy following tumor resection. The analysis demonstrated that immune checkpoint inhibitors significantly improved key clinical outcomes, including disease-free survival and distant metastasis-free survival. However, no clear improvement in overall survival was observed across studies. The study also identified a reduction in recurrence and metastasis risk, supporting the role of these therapies in early-stage cancer management. At the same time, variability across tumor types suggests that benefits may differ depending on cancer subtype and patient population. “Adjuvant PD-1 and PD-L1 inhibitors improve disease-free and distant metastasis-free survival in selected patients with high-risk solid tumors.” In terms of safety, the findings highlight an increased incidence of adverse events associated with PD-1/PD-L1 inhibitors, including fatigue, nausea, pruritus, and hypothyroidism, emphasizing the importance of careful monitoring during treatment. The authors conclude that while PD-1/PD-L1 inhibitors offer meaningful benefits in reducing recurrence and metastasis in high-risk solid tumors, the clinical benefit must be balanced against higher toxicity rates. Future research is needed to refine patient selection, evaluate long-term survival outcomes, and better understand differences across tumor types to optimize the use of these therapies in clinical practice. DOI - https://doi.org/10.18632/oncotarget.28855 Correspondence to - Dhai Almuteri - d.almuteri@qu.edu.sa Abstract video - https://www.youtube.com/watch?v=4Ce07bHfjB4 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28855 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, PD-1, PD-L1, adjuvant immunotherapy, solid tumor To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancers — Microlearning Activity 2: Proceedings from a Session Held Adjunct to the 2026 ASCO GI Cancers Symposium

Play Episode Listen Later Apr 3, 2026 22:10

Featuring perspectives from Dr Jaffer A Ajani, Dr Samuel J Klempner, Dr Rutika Mehta and Dr John Strickler, moderated by Dr Klempner, including the following topics: Older patient with metastatic claudin 18.2-positive gastroesophageal (GE) cancer (0:00) Management of nausea and vomiting with zolbetuximab for GE cancer (9:37) Younger patient with metastatic claudin 18.2-positive, PD-L1-positive GE cancer (15:34) CME information and select publications

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The Future of HNSCC: Aligning Teams, Transforming Care

ReachMD CME

Play Episode Listen Later Mar 31, 2026 15:30

CME credits: 0.25 Valid until: 02-04-2027 Claim your CME credit at https://reachmd.com/programs/cme/The-Future-of-HNSCC-Aligning-Teams-Transforming-Care/54394/ This activity reviews data from the KEYNOTE-689 and NIVOPOSTOP trials evaluating perioperative immune checkpoint inhibition in resectable, locally advanced head and neck squamous cell carcinoma (HNSCC). Experts examine trial design, efficacy outcomes, and the role of PD-L1 combined positive score (CPS) in patient selection. Drs. Uppaluri and Lee discuss how surgical, medical, and radiation oncology teams can coordinate treatment sequencing and integrate perioperative pembrolizumab into practice for patients with locally advanced HNSCC.=

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S16 Ep36: New Trials and Targeted Approaches Advance the Precision of GI Cancer Care: With John Marshall, MD; and Christopher Lieu, MD

Play Episode Listen Later Mar 27, 2026 18:57

In today's episode, we sat down with John Marshall, MD, and Christopher Lieu, MD, to discuss the clinical relevance of KRAS G12C and pan-RAS inhibitors in the management of pancreatic and colorectal cancers. Dr Marshall is chief of Hematology and Oncology, a professor of medicine and oncology, and director of the Otto J Ruesch Center for the Cure of Gastrointestinal Cancers at the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. Dr Lieu is a professor of medicine, associate director for Clinical Research, and co-director of Gastrointestinal Medical Oncology at the University of Colorado Anschutz and the University of Colorado Cancer Center in Aurora. In our exclusive interview, the experts highlighted historical challenges in targeting RAS mutations, as well as recent breakthroughs. They also emphasized the importance of testing early for biomarkers like Claudin 18.2, PD-L1, HER2, and microsatellite instability in patients with gastroesophageal cancers. Furthermore, the experts discussed the need to use targeted therapies early in treatment to avoid treatment resistance, and noted the potential of novel RAS inhibitors and immunotherapies. Their conversation also touched on the importance of rebiopsy and the challenges of obtaining sufficient tissue for biomarker analysis.

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Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancers — Microlearning Activity 1: Proceedings from a Session Held Adjunct to the 2026 ASCO GI Cancers Symposium

Play Episode Listen Later Mar 24, 2026 24:56

Featuring perspectives from Dr Jaffer A Ajani, Dr Samuel J Klempner, Dr Rutika Mehta and Dr John Strickler, moderated by Dr Klempner, including the following topics: Younger patient with metastatic HER2-positive, PD-L1-positive gastric cancer (0:00) Older patient with metastatic HER2-positive gastroesophageal (GE) cancer (8:13) Clinical applications for zanidatamab in GE cancer (13:58) CME information and select publications

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Ep. 127: “MAIT Cell Responses” Featuring Dr. Mansour Haeryfar

The Immunology Podcast

Play Episode Listen Later Mar 24, 2026 69:31

Guest: Dr. Mansour Haeryfar is a Professor in the Department of Microbiology & Immunology at Western University. The Haeryfar Lab is dedicated to advancing our understanding of both conventional and innate-like invariant T cell responses in health and disease. Their research focuses on mucosal-associated invariant T (MAIT) cells, with particular emphasis on exploring their therapeutic potential across a range of conditions. Featured Products and Resources: Explore scientific resources for your immunology research. Download a free wallchart on the production of CAR T cells. The Immunology Science Round Up Immune Imprinting Limits Flu Protection – Early flu infections imprint the immune system, biasing later responses and reducing effectiveness against new strains. Maternal Immunity Protects Newborns – Newborns with E. coli sepsis lack protective maternal antibodies, and maternal priming can provide protection. Building the Anti-Carbohydrate Repertoire – Anti-carbohydrate antibodies develop after birth into a diverse, antigen-shaped B cell repertoire. Engineering Better CAR T Responses – CAR T resistance to checkpoint therapy can be overcome by restoring c-Jun alongside PD-L1 blockade. Image courtesy of Dr. Mansour Haeryfar. Subscribe to our newsletter! Never miss updates about new episodes. Subscribe

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Evolving Treatment Landscape of HER2+ Upper GI Cancer

Dr. Baliga's Internal Medicine Podcasts

Play Episode Listen Later Mar 23, 2026 20:48

Welcome to the Oncology Brothers podcast! In this episode, we dived deep into the current treatment landscape for frontline HER2-positive gastroesophageal junction (GEJ) and gastric cancer. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Apple Podcast: https://podcasts.apple.com/us/podcast/oncology-brothers-practice-changing-cancer-discussions/id1653340966 Follow us on social media: X/Twitter: https://twitter.com/oncbrothers Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ Join us as we welcome Dr. Sunnie Kim from the University of Colorado and Dr. Samuel Cytryn from Memorial Sloan Kettering, who shared their insights on the latest advancements in HER2-targeted therapies. We discussed the pivotal TOGA and KEYNOTE-811, the promising data from the HERIZON-GEA01 study featuring Zanidatamab, and the implications of these findings for clinical practice. Key topics included: Current standard of care for HER2-positive GEJ and gastric cancer The role of PD-L1 status in treatment decisions Mechanisms and efficacy of Zanidatamab compared to traditional therapies Management of side effects, including diarrhea and infusion-related reactions Future directions in HER2-targeted therapies, including T-DXd based on the DESTINY Gastric-04 trial Don't forget to like, subscribe, and hit the notification bell for more updates on treatment algorithms, FDA approvals, and conference highlights! Accreditation/Credit Designation Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians' Education Resource®, LLC designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Acknowledgment of Commercial Support This activity is supported by an educational grant from Jazz Pharmaceuticals, Inc. Link to gain CME credits from this activity: https://www.gotoper.com/courses/new-precision-strategies-for-her2-gea-interpreting-new-data-to-inform-clinical-practice

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Thymus: Aging, Immunity and Longevity

Play Episode Listen Later Mar 20, 2026 5:27

The thymus—long dismissed as vestigial in adults—re-emerges as a powerful biomarker of health and therapeutic response. Two Nature (2026) studies demonstrate that AI-derived thymic health independently predicts all-cause mortality, cardiovascular death, and cancer risk, while also forecasting immunotherapy outcomes across tumor types—performing comparably to PD-L1 and tumor mutation burden. This reframes aging as an immunologic continuum. The thymus may not just reflect health—it may define it. #PrecisionMedicine #Immunology #CardioOncology #AIinMedicine

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Checkpoint Change: Rethinking How PD-1/PD-L1 Inhibitors Are Delivered

VerifiedRx

Play Episode Listen Later Mar 17, 2026 12:28

Immune checkpoint inhibitors targeting PD-1 and PD-L1 have transformed the treatment landscape across a wide variety of cancers, becoming foundational therapies in oncology. Dr. Stacey Sobocinski and Dr. Michele Rice join host Dr. Kerry Schwarz to discuss what the new subcutaneous PD-1/PD-L1 immune checkpoint inhibitors could mean for oncology practice. They cover the three agents that have become available in subcutaneous formulations, their advantages and disadvantages, other important operational, financial, clinical, and safety issues for health systems to consider. Guest speaker:  Stacey Sobocinski, Pharm.D., BCPS Associate Director, Pharmacy Medication Management & Informatics MD Anderson Cancer Center Michele Rice, Pharm.D., BCOP Senior Consulting Solutions Director Vizient Pharmacy Enterprise Solutions Host:  Kerry Schwarz, Pharm.D., MPH Senior Clinical Manager, Evidence-Based Medicine and Outcomes Vizient Center for Pharmacy Practice Excellence  Show Notes: 00:05 — Introduction Announcer welcomes listeners to VerifiedRx, produced by the Vizient Center for Pharmacy Practice Excellence. 00:14 — Episode Overview Host Kerry introduces the topic: new subcutaneous formulations of PD-1 and PD-L1 immune checkpoint inhibitors. These therapies have traditionally been administered intravenously (IV) in infusion centers. Recently approved subcutaneous versions include: Pembrolizumab (Keytruda Qlex) Nivolumab (Opdivo Qvantig) Atezolizumab (Tecentriq Hybreza) Potential benefits include shorter administration times and relief for infusion centers operating at capacity. Guests: Stacy Sobacinski, Associate Director of Pharmacy Medication Management and Informatics, MD Anderson Cancer Center Michelle Rice, Senior Pharmacy Enterprise Solutions Director, Vizient 01:39 — Clinical Data: Efficacy, Safety & Pharmacokinetics Subcutaneous formulations were approved in combination with hyaluronidase, allowing full-dose subcutaneous administration. Clinical studies demonstrated: Comparable pharmacokinetics Similar efficacy Similar safety profiles compared to IV formulations The main difference observed was local injection site reactions, expected with subcutaneous administration. 02:32 — Confidence in Clinical Comparisons Although direct head-to-head trials are limited, extensive experience with IV formulations supports confidence in safety and efficacy. Differences largely relate to administration method, not drug activity. 03:11 — Operational Impact: Changes to Workflow Subcutaneous administration introduces new operational considerations. Shorter injection times may appear advantageous, but real-world workflow impact is still being evaluated Much of a patient's visit still involves: Waiting room time Laboratory testing Provider visits Care coordination 04:06 — Chair Time vs Total Visit Time For therapies previously requiring longer infusions, switching to subcutaneous injections can significantly reduce chair time. For therapies previously infused over 30 minutes, the difference between IV and subcutaneous administration time may be less impactful. 04:24 — Administration Challenges Subcutaneous doses are not small-volume injections. Injection volumes may reach 10–15 mL Nursing considerations include: Patient tolerance for larger-volume injections. IV infusions allow nurses to start the infusion and attend to other tasks. Subcutaneous injections require continuous nursing presence during administration. This may increase direct nursing time. 05:05 — Equipment Considerations Some centers may use syringe pumps to administer subcutaneous injections. Many adult infusion centers do not currently have pumps since chemotherapy is typically delivered via IV using infusion pumps. Implementing syringe pumps could require additional equipment and associated procedures. 05:32 — Operational Complexity Transitioning to subcutaneous therapy involves more than simply switching order sets. Organizations must evaluate: Staffing models Nursing workflows Equipment availability Infusion center capacity management. 06:25 — Financial Considerations Subcutaneous formulations are currently priced roughly at parity with IV versions. Manufacturers may be incentivized to transition providers to subcutaneous formulations before biosimilars enter the market. 07:07 — Anticipating Market Dynamics Over time, pricing strategies may shift to encourage broader adoption. Biosimilar competition for these agents is expected within the next few years. 07:11 — Site of Care Considerations Adoption may vary by care setting: Hospital outpatient departments Physician offices Freestanding infusion centers 08:06 — Strategic Timing Decisions Health systems may weigh: Operational advantages of subcutaneous administration Potential cost reductions from future biosimilars Some organizations may delay adoption until biosimilar competition arrives. 08:24 — Infusion Center Optimization Subcutaneous therapies could increase turnover. Some centers may develop “express lanes” for subcutaneous administration. 09:01 — Payer Influence If subcutaneous formulations are perceived as cheaper or operationally simpler, payers may: Restrict site of care Prefer administrations in physician offices or non-hospital settings. 09:45 — Key Questions for Health Systems Organizations should consider: What value does the new dosage form provide? Which patients benefit most from subcutaneous administration? How will payer policies evolve? 10:05 — Evaluating Clinical Value Institutions often approach new dosage forms with caution. Subcutaneous PD-1/PD-L1 inhibitors may not offer the administration time reductions seen with other biologics because there is not as large of a difference in administration times (30 minutes versus 5 minutes). 10:53 — Patient Selection Considerations Subcutaneous formulations may be most beneficial for patients: Receiving monotherapy With difficult IV access Patients receiving combination therapies may see less benefit since IV access is already required. 11:12 — Additional Patient Factors Some patients have low body mass or cachexia, making high-volume subcutaneous injections more difficult. Physicians may prefer individualized treatment decisions rather than blanket formulary changes. 11:33 — Final Thoughts Transitioning to subcutaneous PD-1/PD-L1 inhibitors involves clinical, operational, and financial considerations. Observation times, administration practices, and workflow models continue to evolve. Ongoing monitoring of emerging best practices is encouraged. 12:15 — Closing ongoing monitoring of emerging best practices. Listeners are invited to subscribe and follow VerifiedRx for future episodes. Subscribe Today! Apple Podcasts Spotify YouTube RSS Feed

Journal Club: Five Papers Pushing the Boundaries of Metabolic Therapy | The Metabolic Link Ep. 89

The Metabolic Link

Play Episode Listen Later Mar 3, 2026 68:38

Get free access to our new Ketogenic Metabolic Therapy ebook here.Could changing your metabolism reduce alcohol cravings, ease psychiatric symptoms, and even make cancer immunotherapy more effective? The science is pointing to yes, and the mechanisms are fascinating.In this Journal Club episode, co-hosts Victoria Field, Dr. Dominic D'Agostino, and Dr. Angela Poff break down five peer-reviewed papers from their newly released Ketogenic Metabolic Therapy ebook (Volume 4). From a French preclinical study showing ketogenic diet enhances PD-L1 immunotherapy response in kidney cancer, to an NIH/UPenn trial using machine-learning-derived fMRI signatures to measure reduced alcohol cravings during ketosis, to Stanford's pilot trial demonstrating notable metabolic and psychiatric improvements in schizophrenia and bipolar disorder, this episode covers the cutting edge of metabolic therapy research.Questions Answered in This Episode:Why does the brain crave alcohol in people with alcohol use disorder, and how might ketones help? How might a ketogenic diet affect a tumor's response to immunotherapy?Can insulin resistance in the brain contribute to psychiatric symptom severity?How does the ketogenic diet compare to the Mediterranean diet for autoimmune inflammation?Does timing of ketogenic diet initiation matter for chronic pain relief?Is it realistic for people with serious mental illness to adhere to a ketogenic diet?Whether you're a clinician, researcher, or someone looking to understand the latest science, this episode reveals just how far-reaching ketogenic metabolic therapy has become, spanning oncology, psychiatry, addiction, autoimmune disease, chronic pain, and much more!In every episode of The Metabolic Link, we'll uncover the very latest research on metabolic health and therapy. If you like this episode, please share it, subscribe, follow, and leave us a comment or review on whichever platform you use to tune in!You can find us on all your major podcast players here and full episodes are also up on our Metabolic Health Summit YouTube channel!Find us on social: Instagram Facebook YouTube LinkedIn Please keep in mind: The Metabolic Link does not provide medical or health advice, but rather general information that does not serve as a substitute for a licensed healthcare professional. Never delay in seeking medical advice from an appropriately licensed medical provider for any health condition that you may have.

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Combination Approaches in PD-L1–Positive Metastatic Triple Negative Breast Cancer

spotify australia positive approaches ascent combination immunotherapy metastatic triple negative breast cancer adcs pd l1 tnbc

Play Episode Listen Later Mar 2, 2026 24:33

Welcome to the Oncology Brothers podcast! In this episode, we dived into the evolving frontline treatment landscape for triple-negative breast cancer (TNBC). Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: •⁠ ⁠X/Twitter: https://twitter.com/oncbrothers •⁠ ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ Join us as we welcomed Dr. Sherene Loi, a leading breast medical oncologist from Australia, to discuss the challenges of treating TNBC and the exciting new treatment options available. We explored the significance of PD-L1 scoring in metastatic TNBC, the implications of recent trials like ASCENT-04, and the potential of antibody-drug conjugates (ADCs) such as sacituzumab govitecan and datopotamab deruxtecan. Key topics included: • The role of PD-L1 positivity in treatment decisions • Insights from the ASCENT-04 trial and its findings • Common side effects associated with sacituzumab and strategies for management • The future of immunotherapy and ADCs in TNBC treatment Whether you're a healthcare professional or someone interested in the latest advancements in oncology, this episode is packed with valuable information and clinical pearls. Don't forget to subscribe for more insightful discussions on cancer treatment! #TNBC, #PDL1positive, #ASCENT04, #Immunotherapy, #OncBrothers

S16 Ep15: Six-Year CheckMate 9LA Data Reinforce Durable Survival in Metastatic NSCLC: With David Carbone, MD, PhD

Play Episode Listen Later Feb 26, 2026 12:28

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

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S16 Ep14: Pumitamig Represents Potential Immunotherapy Strategy for TNBC: With Sarah Sammons, MD

strategy massachusetts md harvard medical school represents immunotherapy dana farber cancer institute sammons pd l1 tnbc

Play Episode Listen Later Feb 26, 2026 10:47

In today's episode, we sat down with Sarah Sammons, MD. Dr Sammons is associate director of the Metastatic Breast Cancer Program and a senior physician at Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, both in Boston, Massachusetts.In our exclusive interview, Dr Sammons discussed the rationale for and findings from a phase 2 study (NCT06449222) evaluating the PD-L1– and VEGF-A–directed bispecific antibody pumitamig (BNT327/BMS986545) in patients with locally advanced or metastatic triple-negative breast cancer (TNBC), as well as what these data may mean for the TNBC treatment paradigm.

Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer Guideline Update

ASCO Guidelines Podcast Series

Play Episode Listen Later Feb 26, 2026 28:55

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.

Atezolizumab, Bevacizumab, and Non-Platinum Chemotherapy for PROC

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Feb 23, 2026 6:21

In this episode of JCO Article Insights, host Dr. Melis Canturk summarizes the article, "Atezolizumab With Bevacizumab and Nonplatinum Chemotherapy for Recurrent Ovarian Cancer: Final Results From the Placebo-Controlled AGO-OVAR 2.29/ENGOT-ov34 Phase III Trial," by Harter et al. TRANSCRIPT Melis Canturk: Hello, and welcome to the JCO Article Insight. I'm your host, Melis Canturk, and today we will be discussing the JCO article, "Atezolizumab With Bevacizumab and Nonplatinum Chemotherapy for Recurrent Ovarian Cancer: Final Results From the Placebo-Controlled AGO-OVAR 2.29/ENGOT-ov34 Phase III Trial." While integrating immune checkpoint inhibitors has revolutionized the treatment of various gynecologic cancers, these agents have historically shown limited single agent activity in ovarian cancer. Despite a strong biological rationale for combining immunotherapy with chemotherapy and bevacizumab to enhance T-cell infiltration and normalized tumor vasculature, several phase III trials have failed to demonstrate a significant survival benefit in this setting. The AGO-OVAR 2.29/ENGOT-ov34 trial was launched to definitely evaluate whether adding the PD-L1 inhibitor atezolizumab to this combination could improve long-term outcomes for patients experiencing early relapse. This international, double-blind, randomized phase III trial enrolled 574 patients with epithelial ovarian, fallopian tube, or peritoneal cancer. Eligible participants had to be in their first or second relapse within 6 months of completing platinum therapy or in their third relapse regardless of the treatment-free interval. All patients received bevacizumab and an investigator selected chemotherapy backbone, either paclitaxel or doxorubicin. They were randomly assigned to receive either 840 mg of atezolizumab or a placebo every 2 weeks until disease progression or for a maximum of 2 years. The study population was an all-comer group, though patients were stratified by their PD-L1 status, previous bevacizumab use, and the number of prior treatment lines. The trial did not meet its primary end points, as the addition of atezolizumab failed to significantly improve overall survival or progression-free survival in the intention-to-treat population. For the primary end point of overall survival, the median was 14.2 months with atezolizumab compared to 13 months with the placebo. Progression-free survival was similarly insignificant, with a median of 6.4 months in the experimental arm versus 6.7 months in the control arm. Furthermore, the objective response rates were nearly identical between the groups, recorded at 40% for atezolizumab and 44% for the placebo. Interestingly, exploratory subgroup analyses revealed potential signals of benefit in specific populations, even though the overall trial was negative. Patients who had been previously treated with bevacizumab appeared to derive a greater benefit from the addition of atezolizumab than those who were bevacizumab-naïve. Additionally, outcomes seemed more favorable for patients receiving a paclitaxel chemotherapy backbone compared to those receiving doxorubicin. However, PD-L1 status did not appear to be a predictive marker for success, as hazard ratios for survival were similar regardless of whether the tumor was PD-L1 positive or negative. The safety profile of the triple combination was consistent with the known toxicities of the individual drugs. Grade 3 or higher adverse events occurred in 73% of the atezolizumab group and 70% of the placebo group. While the experimental arm saw higher incidences of immune-mediated events, such as thyroid-related issues, these were generally manageable. Serious adverse events were more frequent in the atezolizumab arm than in the placebo arm, but discontinuation rates due to toxicity were relatively low and comparable between the two groups. In conclusion, the AGO-OVAR 2.29 trial confirms that adding atezolizumab to bevacizumab and nonplatinum chemotherapy does not provide a statistically significant survival advantage for patients who receive nonplatinum chemotherapy for recurrent ovarian cancer. This study contributes to the growing body of evidence showing that immune checkpoint inhibitors have yet to find a definitive role in the standard treatment of recurrent ovarian cancer. Future research will likely focus on more sophisticated molecular stratification and the use of novel agents, such as bispecific antibodies, to overcome the challenging tumor microenvironment of low-grade serous ovarian cancer. Thank you for tuning into JCO 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.

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S1 Ep202: From Cold to Hot: Navigating a New Frontier of Breast Cancer Immunotherapy

Oncology Peer Review On-The-Go

Play Episode Listen Later Feb 23, 2026 26:33

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

184: Digital Pathology Guidelines: What Every Lab Must Get Right

Medical Sales U with Dave Sterrett

Play Episode Listen Later Feb 20, 2026 34:27 Transcription Available

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

E43 | Nurse to Oncology Educator at Eversana

Play Episode Listen Later Feb 16, 2026 42:15

Is it time to trade your scrubs for a corporate career? In this episode, we sit down with Sydney Gramuglia, a Registered Nurse who successfully transitioned from bedside burnout to a high-impact, 6-figure role as an Oncology Clinical Educator at Eversana partnering with Sun Pharma. Sydney didn't have prior sales experience, and the job she landed wasn't even listed in her state—but she beat out veteran candidates anyway. Today, we're pulling back the curtain on the "Medical Sales U" blueprint she used to master a grueling 5-round interview process and land her dream job in the pharmaceutical industry.INSIDE THIS EPISODE:*The "Experience" Myth: Why "not enough experience" is usually a cover for "not enough preparation."*The LinkedIn Transformation: How Sydney went from 20 connections to 500+ and got headhunted by hiring managers.*The Mock Presentation: The exact 40-step rehearsal strategy Sydney used to master complex MOA (Mechanism of Action) and PD-L1 pathways.*Clinical Educator vs. Sales: Understanding the different paths for nurses in pharma.*The Contract Partnership: How the Eversana and Sun Pharma collaboration works.CHAPTERS:0:00 – Meet Sydney: From Bedside Nurse to Pharma Pro2:15 – The "Depressing" Reality of Nursing during COVID5:00 – Finding a Passion for Oncology7:30 – Why Your LinkedIn Profile Is Your New Resume9:15 – Breaking Down the Sun Pharma Offer13:45 – Clinical Educator vs. Sales: Which is right for you?16:10 – The Brutal Rejection that changed everything23:50 – Preparing for the 5-Round Interview Gauntlet25:30 – How to Ace a Mock Clinical Presentation31:00 – The Power of the Medical Sales U Community36:45 – Lifestyle Design: The perks of a corporate clinical role39:30 – Exploring Charleston: Best food & dog-friendly spotsCONNECT WITH Sydney Gramuglia - https://www.linkedin.com/in/sydney-gramuglia/READY TO BREAK INTO MEDICAL SALES? We help professionals transition into top-tier medical sales roles: medicalsalesu.com/#MedicalSales #NurseCareerChange #PharmaJobs #ClinicalNurseEducator #MedicalSalesU #NursingBurnout #CareerPivot #SunPharma #Eversana #MedicalDeviceSales #HealthcareInnovation

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Therapy for Stage IV NSCLC Without Driver Alterations: ASCO Living Guideline Update 2026.3.0 Part 1

ASCO Guidelines Podcast Series

Play Episode Listen Later Feb 3, 2026 18:03

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.

Therapy for Stage IV NSCLC With Driver Alterations: ASCO Living Guideline Update 2026.3.0 Part 2

ASCO Guidelines Podcast Series

Play Episode Listen Later Feb 3, 2026 19:36

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.

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S15 Ep37: Immuno-Oncology and Novel Cell Therapies Set Transformation in Motion for Gynecologic Oncology: With Ursula A. Matulonis, MD; and Rebecca Porter, MD, PhD

phd transformation massachusetts md treatments car motion cart harvard medical school therapies md phd dana farber cancer institute pd l1 tme gynecologic oncology immuno oncology ctdna

Play Episode Listen Later Jan 28, 2026 30:39

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.In this episode, Dr Matulonis sat down with guest Rebecca Porter, MD, PhD. Dr Porter is a physician at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School.Drs Matulonis and Porter discussed the evolving role of immunotherapy in gynecologic cancer management, focusing on recent clinical breakthroughs and future directions. They noted that although high-grade serous ovarian cancer has historically been refractory to immunotherapy, the phase 3 KEYNOTE-B96 trial (NCT05116189) demonstrated an efficacy benefit with the addition of pembrolizumab to weekly paclitaxel for patients with platinum-resistant disease. In particular, improvements in overall survival were noted in the PD-L1–positive patient population. Dr Porter attributed this success to the metronomic weekly dosing of paclitaxel, which may increase neoantigen levels and favorably alter the tumor microenvironment (TME).Moreover, the experts highlighted how immunotherapy has already become the standard of care for patients with mismatch repair–deficient advanced or recurrent endometrial cancer. However, they explained that for the mismatch repair–proficient population, this benefit is less clear and appears most significant in patients with measurable disease or specific molecular subtypes. They added that although circulating tumor DNA (ctDNA) assay results correlate with treatment outcomes, ctDNA is currently not an actionable biomarker for determining treatment duration or selection.Lastly, Drs Matulonis and Porter reported that the field of gynecologic oncology is shifting toward combination therapies and novel platforms beyond standard checkpoint inhibitors. Treatment advances include bispecific and trispecific antibodies that engage multiple cell types or signals; as well as adoptive cellular therapies, such as CAR T-cell and CAR natural killer–cell therapies. Ultimately, the experts concluded that the goal of managing challenging-to-treat diseases like ovarian cancer is to use combinatorial approaches—incorporating vaccines, anti-angiogenic therapies, and chemotherapy—to overcome the immunosuppressive nature of the TME.

Head & Neck Cancers Treatment Landscape & Algorithm – Dr. Fangdi Sun

head cancer treatments landscape stanford university algorithms neck hpv immunotherapy ebv pd l1

Play Episode Listen Later Jan 26, 2026 23:34

In this episode of the Oncology Brothers podcast, we dived into the current treatment landscape for head and neck cancer. We welcomed Dr. Fangdi Sun, a head and neck medical oncologist from Stanford University, to discuss key topics including: • The importance of initial workup and the role of biomarkers, including HPV and EBV testing. • Treatment paradigm for early-stage and locally advanced head and neck cancers, focusing on the differences between HPV-positive and HPV-negative disease. • The evolving role of immunotherapy and the new perioperative approaches in treatment. • Insights into managing metastatic disease, including the use of PD-L1 scores and systemic therapy options. • The significance of multidisciplinary collaboration in optimizing patient care. Whether you're a healthcare professional or simply interested in oncology, this episode provides valuable insights into the complexities of head and neck cancer treatment. Don't miss out on this informative discussion! Follow us on social media: •⁠ ⁠X/Twitter: https://twitter.com/oncbrothers •⁠ ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ Subscribe to our channel for more episodes as we continue to bridge the gap in oncology! #HeadAndNeckCancer, #HPV, #Immunotherapy, #MultidisciplinaryCare, #OncologyBrothers

252. Astaxanthin, Inflammation, and the Science of Survival: A Physicist's Journey Beyond Terminal Cancer with Samuel Shepherd

Rewiring Health

Play Episode Listen Later Jan 20, 2026 95:38

What if inflammation—not genetics, not aging, not bad luck—was the common thread behind most chronic disease?In this expansive and thought-provoking conversation, physicist, inventor, and engineer Samuel Shepherd shares his extraordinary personal journey after being diagnosed with a rare, terminal bone marrow cancer in 2003. Given no viable medical options, Sam turned to decades of scientific expertise to investigate inflammation, free radicals, and cellular breakdown—ultimately leading him to study astaxanthin, one of the most powerful antioxidants found in nature.We explore the science of oxidative stress, PD-L1 immune signaling, cellular transport, and why conventional antioxidant delivery often fails. Sam explains how he developed a patented glycosidic form of astaxanthin designed to improve absorption and target inflammation more effectively—and how this work reshaped not only his health, but his entire understanding of disease, aging, and resilience.This episode also dives into:Why inflammation may be the root driver of many chronic and neurodegenerative conditionsThe role of free radicals in cancer, Parkinson's, Alzheimer's, and metabolic diseaseHow modern diets—especially fructose exposure—impact inflammation over timeWhat HS-CRP can reveal about long-term health riskWhy curiosity, self-trust, and asking better questions matter more than blind complianceThis is not medical advice. It is an invitation into inquiry, responsibility, and deeper self-education—especially for those who sense that healing requires more than symptom management.If you're someone who values science, autonomy, and understanding your body rather than outsourcing it, this conversation will expand how you think about health, inflammation, and what's truly possible.Connect with Samuel: Website: https://valasta.net/ Youtube: https://www.youtube.com/@ValAsta Facebook: https://www.facebook.com/ValastaHome Connect with Kelly:⁠⁠⁠drkellykessler.com⁠⁠⁠Free Guide: Sacred Boundaries: ⁠⁠⁠http://drkellykessler.com/sacredboundaries⁠⁠Self-Respect Reset is a guided, body-based experience for women who struggle to set boundaries—not because they don't know what they need, but because it hasn't felt safe to honor it.Inside, you'll learn how to rebuild inner safety, strengthen self-trust, and create boundaries that actually protect your peace—without guilt, over-explaining, or self-abandonment.

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