Podcasts about ctdna

Oncology Peer Review On-The-Go

Play Episode Listen Later Jun 5, 2026 22:38

Featuring perspectives from Prof Thomas Powles, including the following topics: Circulating tumor DNA (ctDNA) analyses with adjuvant nivolumab for MIBC in the CheckMate 274 study (0:00) Use of ctDNA to guide response-adapted bladder preservation for patients with MIBC (2:27) ctDNA response-adapted treatment de-escalation for patients with metastatic urothelial carcinoma: The CT-READ trial (10:26) Emerging data and studies regarding urinary tumor DNA (18:04) CME information and select publications

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Amerikanischer Krebskongress 2026 – Bilanz aus Chicago: Was die Onkologie bewegt

ExpertenDialoge

Play Episode Listen Later Jun 3, 2026 12:48 Transcription Available

Harald Müller-Huesmann, Kerstin Milicic-Ouakili und David Liesenfeld ziehen Bilanz aus Chicago: Im Fokus stehen die KRAS-Inhibition, ctDNA, Präzisionsmedizin, Prävention und die Frage, wie neue Erkenntnisse schneller in die Versorgung gelangen.

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Amerikanischer Krebskongress 2026 – Update Senologie: Deeskalation, ctDNA und neue endokrine Strategien

ExpertenDialoge

Play Episode Listen Later Jun 2, 2026 12:00

Harald Müller-Huesmann spricht mit Maggie Banys-Paluchowski über aktuelle ASCO-Daten zum Mammakarzinom: neue Erkenntnisse zur axillären Chirurgie nach neoadjuvanter Therapie, Genexpressionstests zur Chemotherapieentscheidung, ctDNA-basiertes Therapiemonitoring und neue endokrine Strategien.

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S1 Ep216: How the Landscape of GI Oncology is Evolving | A 2026 ASCO Preview

Play Episode Listen Later May 28, 2026 29:06

In a recent interview with CancerNetwork®, Nicholas Hornstein, MD, PhD, an assistant professor at the Donald and Barbara Zucker School of Medicine of Hofstra University and Northwell Health, discussed emerging data and clinical shifts in the care of patients with gastrointestinal (GI) cancers ahead of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.Advancements in Colorectal CancerHornstein highlighted the increasing integration of targeted therapies into the first-line setting for patients with colorectal cancer (CRC). For those with BRAF V600E-mutated metastatic disease, data from the phase 3 BREAKWATER trial (NCT04607421) support moving targeted therapy into the first line.1 He noted that initiating these therapies early is critical, as a significant percentage of patients may experience rapid clinical decline and lose the opportunity for second-line treatment if targeted options are delayed.In the HER2-positive space, clinicians currently utilize tucatinib (Tukysa)-based regimens or fam-trastuzumab deruxtecan-nxki (Enhertu). Hornstein also anticipated the arrival of bispecific antibodies, such as zanidatamab-hrii (Ziihera), which are expected to gain approval in upper GI cancers before moving into the CRC landscape.The Role of ctDNA and Pancreatic CancerRegarding localized disease, Hornstein discussed the potential for circulating tumor DNA (ctDNA) to guide adjuvant therapy for patients with stage II colon cancer. Data from trials like CIRCULATE (NCT05174169) are expected to further clarify how ctDNA can assist in the escalation or de-escalation of treatment.2 In pancreatic cancer, the phase 3 RASolute 302 trial (NCT06625320) investigating daraxonrasib is poised to change the standard of care for patients with second-line pancreatic cancer immediately upon an anticipated regulatory approval.3Barriers to Precision MedicineA primary unmet need that Hornstein identified was the low rate of biomarker testing; currently, only about half of patients with metastatic disease receive necessary sequencing or microsatellite instability testing. Hornstein emphasized that multidisciplinary cooperation and improved systems are essential to ensure all patients with targetable mutations receive appropriate care. Finally, he highlighted the development of large language model tools to assist clinicians with data ingestion and clinical trial matching.References1. Kopetz S, Wasan HS, Yoshino T, et al. BREAKWATER: primary analysis of first-line (1L) encorafenib + cetuximab (EC) + FOLFIRI in BRAF V600E-mutant metastatic colorectal cancer (mCRC). J Clin Oncol. 2026;44(suppl 2):13. doi:10.1200/JCO.2026.44.2_suppl.132. Dasari A, Yu G, Kopetz S, et al. NRG-GI008: colon adjuvant chemotherapy based on evaluation of residual disease (CIRCULATE-NORTH AMERICA). J Clin Oncol. 2026;44(suppl 16):TPS3686. doi:10.1200/JCO.2026.44.16_suppl.TPS36863. Wolpin B, Wainberg ZA, Hendifar A, et al. Daraxonrasib, a RAS(ON) multi-selective inhibitor vs chemotherapy in previously treated metastatic pancreatic adenocarcinoma (mPDAC): Primary and final analysis from the phase 3 RASolute 302 study. J Clin Oncol. 2026;44(suppl 17):LBA5. doi:10.1200/JCO.2026.44.17_suppl.LBA5

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Genitourinary Cancers — 5-Minute Journal Club Issue 1 with Professor Thomas Powles: Current and Future Role of Tumor-Informed Circulating Tumor DNA Assays

Play Episode Listen Later May 27, 2026 29:57

Interview conducted on March 11, 2026, by Dr Neil Love, including the following topics: Circulating tumor DNA (ctDNA)-guided adjuvant therapy with atezolizumab for muscle-invasive bladder cancer (MIBC) (0:00) Use of ctDNA in guiding systemic treatment selection for patients with urothelial bladder cancer (10:03) ctDNA analyses with perioperative durvalumab for MIBC in the Phase III NIAGARA study (16:51) New research advances in the monitoring and management of urothelial bladder cancer (22:21) CME information and select publications

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BCL2 & HER2 Targeting Agent Updates

OncoPharm

Play Episode Listen Later May 21, 2026 13:45

The FDA has been a bunch of busy bees with new approvals: 1. Sonrotoclax, an exciting new BCL2 inhibitor approved for 3rd-line Mantle Cell Lymphoma 2. An all PO regimen of decitabine/cedazuridine + venetoclax is approved for AML. 3. Zenoctuzumab gets an FDA approval for cholangiocarcinoma with an efficacy patient population = 19 4. T-DXd is a good drug and continues to pile on FDA approvals 5. Adjuvant atezolizumab in bladder cancer is approved in conjunction with ctDNA serial monitoring to determine who gets treatment Check out the Oncology Insights Newsletter: www.kelleycpharmd.com/newsletter-oncopharm

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Ep. 644 Optimizing Liver Transplant Pathways and Decision-Making with Dr. Neil Mehta and Dr. Ari Cohen

BackTable Podcast

Play Episode Listen Later May 12, 2026 37:30

A high-functioning HCC tumor board can turn complex transplant decisions into coordinated treatment plans that account for liver reserve, tumor biology, and evolving biomarkers. In this episode of the BackTable Podcast 2026 HCC Creator Weekend™, abdominal transplant surgeon Dr. Ari Cohen (Ochsner Health) and transplant hepatologist Dr. Neil Mehta (UCSF) join host Dr. Kavi Krishnasamy to map out strategies for effective multidisciplinary treatment and transplantation planning in HCC. --- Get the BackTable apphttps://www.backtable.com/app --- This podcast is supported by an educational grant from Sirtex and Boston Scientific. --- Timestamps 00:00 - Introduction00:51 - Starting a Tumor Board06:39 - Building Referral Streams09:03 - Academic and Community Practice Integration14:31 - Treatment Selection Criteria20:38 - Modern HCC Biomarkers25:24 - Role of ctDNA and Biopsy29:37 - Bridging Therapy on Transplant Waitlist32:34 - Downstaging Strategy and Risks39:25 - Final Thoughts and Closing Remarks --- More about this episode The physicians discuss what it takes to build a robust tumor board, from fostering hospital buy-in to engaging leaders across specialties and utilizing virtual formats for consistent participation. The conversation explores clinical decision-making, emphasizing the integration of AFP-L3 and DCP biomarkers alongside AFP to better understand tumor biology and predict post-transplant recurrence. Dr. Mehta and Dr. Cohen also share their patient selection criteria, discussing how bilirubin, liver disease etiology, and INR influence decisions. While radiographic guidance remains central to HCC management, they highlight the growing potential of reliable ctDNA analysis and other biomarkers. The specialists conclude by emphasizing that an integrated, communicative tumor board is the most effective way to navigate the nuances of liver reserve and HCC biology to achieve the best possible patient outcomes. --- Resources Sustained AFP-L3 or DCP expression is associated with progression risk and inferior outcomes in unresectable hepatocellular carcinoma.https://doi.org/10.1007/s10238-025-01877-8 --- BackTable Vascular & Interventional (VI) is the go-to podcast for interventional radiologists, vascular surgeons, and interventional cardiologists. Download the free BackTable app to get early access to new episodes, cases, and courses curated by physicians in your specialty. ► https://www.backtable.com/app

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Through a Patient's Experience | The Eye Believe Podcast

The Eye Believe Podcast

Play Episode Listen Later May 11, 2026 27:11 Transcription Available

In this episode of the Eye Believe Podcast, we're joined by Wendy Carpenter, a metastatic ocular melanoma patient who is currently NED (No Evidence of Disease). Wendy shares her personal experience using ctDNA (circulating tumor DNA) testing as part of her ongoing surveillance and care. She discusses how this blood-based testing helps monitor disease activity, informs conversations with her medical team, and provides another tool for navigating life after treatment. In this conversation, Wendy opens up about: What ctDNA testing is and how it works How she incorporates ctDNA into her surveillance plan The emotional realities of monitoring after metastatic disease Living with hope, uncertainty, and gratitude as an NED survivor Register for Eye on ctDNA Webinar on May 22! https://events.zoom.us/ev/AvuhW89ZCjUP5wdMLqfUIHZv66yDDvXNS4Cws4X9M9okF1pnf-ax~AsOT8AphEb5PJVQjLmAyI6LsBZCgLhHe0tWYJREvI-AbmKVVmO-VUGyvCA Hear more of Wendy's story: Enucleation 101 Panel: https://youtu.be/fmzI_QeB5mM Eye on Mental Health 2026 - patient panel participant (omit this if you can't find the recording or its not up) Information on Signatera: https://www.natera.com/info/monitor-cancer/?utm_source=goog_na_sem&utm_medium=cpc&utm_campaign=4440280632&utm_keyword=bladder-cancer-check&utm_content=natesign_ubr_bladder_na&utm_id=natesign86421&gclsrc=aw.ds&gad_source=1&gad_campaignid=23805042236&gclid=Cj0KCQjwh-HPBhCIARIsAC0p3cdRcVraC3zQMJmLaetu_jgIX2Bt12wY5vs5I6sd8YB13rK8GI-VBnMaAuDVEALw_wcB This episode offers a patient-centered perspective on an evolving area of cancer care and highlights how new technologies are helping empower patients in their journeys.

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S17 Ep20: Biomarker-Directed Therapies Move the GI Oncology Paradigm Beyond a One-Size-Fits-All Approach: With Michael J. Pishvaian, MD, PhD

Play Episode Listen Later May 8, 2026 22:55

Welcome to OncLive On Air®! I'm your host today, Courtney Flaherty.OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions. In today's episode, Michael J. Pishvaian, MD, PhD, sat down to discuss the evolving role of biomarker-directed strategies in gastrointestinal (GI) oncology, as well as the importance of early comprehensive testing to identify molecular drivers and resistance mechanisms when approaching frontline treatment selection and sequencing. Pishvaian serves as director of the Gastrointestinal, Developmental Therapeutics, and Clinical Research Programs for the Johns Hopkins Kimmel Cancer Center in the National Capital Region.Pishvaian began the discussion by highlighting the shift from a disease-site-specific approach to a molecularly defined paradigm, noting that microsatellite instability–high status and NTRK fusions now dictate therapy regardless of tumor origin. He reviewed the transformational data from the phase 3 HERIZON-GE-01 trial (NCT04276493), positing that zanidatamab (Ziihera) could become the new standard of care for HER2-positive upper GI cancers due to unprecedented survival outcomes. He also emphasized the emergence of Claudin 18.2-directed therapies, noting that data from the phase 2 ILUSTRO study (NCT03505320) demonstrates remarkable progression-free survival when adding zolbetuximab (Vyloy) to mFOLFOX6 and nivolumab (Opdivo) for high-expressing subgroups.The conversation then shifted to colorectal cancer, where Dr. Pishvaian detailed how data from the phase 3 BREAKWATER trial (NCT03845036) has "locked in" a paradigm requiring frontline testing for BRAF V600E mutations to guide the use of encorafenib (Braftovi) plus cetuximab (Erbitux). He also discussed the "care revolution" in KRAS inhibition, spotlighting the significant survival benefits seen with daraxonrasib in pancreatic cancer and the potential for novel allele-specific inhibitors to combat disease resistance.Finally, Pishvaian addressed the practicalities of implementation, noting that testing rates in the community remain low. He advocated for prioritizing testing, including liquid biopsies and ctDNA, at the time of initial diagnosis to ensure no patient is left behind.This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.

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Urinary and Circulating Tumor DNA in Muscle-Invasive Bladder Cancer: NIAGARA Data

Project Oncology®

Play Episode Listen Later May 8, 2026 13:30

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Petros Grivas, MD, PhD Could emerging biomarkers redefine how we assess response and recurrence risk in muscle-invasive bladder cancer? To find out, Dr. Charles Turck speaks with Dr. Petros Grivas about the key findings from the phase 3 NIAGARA trial. Together, they explore how perioperative durvalumab impacts circulating tumor DNA (ctDNA) clearance and clinical outcomes, including event-free and overall survival. Their conversation also highlights the prognostic value of ctDNA and the potential for urinary tumor DNA to more closely correlate with pathologic complete response. Dr. Grivas is a Professor in the Division of Hematology and Oncology at the University of Washington School of Medicine, as well as the Clinical Research Division at the Fred Hutchinson Cancer Center, where he's also the Medical Director of the International Program and of local and regional outreach.

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Localized Colorectal Cancer — Microlearning Activity 3: Proceedings from a Session Held Adjunct to the 2026 ASCO GI Cancers Symposium

Play Episode Listen Later May 2, 2026 18:12

Featuring perspectives from Dr Stacey A Cohen, Dr Christopher Lieu and Dr Jenny Seligmann, moderated by Dr Lieu, including the following topics: Role of circulating tumor DNA (ctDNA) testing in the escalation of treatment for Stage II and deescalation for Stage III colon cancer (0:00) Impact of timing on the clinical relevance of ctDNA minimal residual disease test results in localized colorectal cancer (8:58) Approach to managing Stage III colon cancer with ctDNA-positive results after adjuvant treatment (13:35) CME information and select publications

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S17 Ep13: Cases and Conversations: Translating ctDNA Into Clinical Decisions in Breast Cancer

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Play Episode Listen Later Apr 30, 2026 25:59

In this podcast, experts Neil Iyengar, MD; Kelly Elizabeth McCann, MD, PhD; and Wassim Mchayleh, MD, MBA, FACP, discuss the clinical applications and current evidence for using circulating tumor DNA (ctDNA) testing in early-stage and metastatic breast cancer.

ctDNA-Guided Adjuvant Atezolizumab in MIBC: IMvigor011 Insights

Project Oncology®

Play Episode Listen Later Apr 30, 2026 9:00

Host: Charles Turck, PharmD, BCPS, BCCCP Guest: Guru P. Sonpavde, MD What if molecular relapse in muscle-invasive bladder cancer (MIBC) could be detected early enough to better inform treatment decisions? To find out, Dr. Charles Turck speaks with Dr. Guru Sonpavde to explore new IMvigor011 findings presented at the 2026 ASCO Genitourinary Cancers Symposium. Their discussion highlights how ctDNA monitoring identifies early recurrence risk, captures real-time immunotherapy activity, and positions ctDNA clearance as a powerful prognostic marker. Dr. Sonpavde is the Medical Director of Genitourinary Oncology and the Phase I Clinical Research Unit, and the Christopher K. Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute in Orlando.

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Episode 38: Genomics 101 in GU Cancers with Dr. Alex Wyatt

The View on GU | with Lalani and Wallis

Play Episode Listen Later Apr 23, 2026 37:16

In this episode, Dr. Aly-Khan Lalani, Dr. Christopher Wallis, and Dr. Alex Wyatt walk through the fundamentals of clinical genomics and why it matters for routine practice. They discuss which alterations matter in prostate cancer, germline vs. somatic testing, ctDNA test use cases and limits, and more.Dr. Alex Wyatt is an Associate Professor in Urologic Sciences and holds the President's Excellence Chair in Precision Oncology at the University of British Columbia. He is also a Senior Scientist at the Vancouver Prostate Centre and BC Cancer, where his work focuses on advancing clinical genomics and precision oncology in prostate cancer.This podcast has been made possible through unrestricted financial support by Pfizer, Tolmar, AbbVie, Astellas, Eisai, Ipsen, Merck, Bayer, TerSera.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.ca

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How to Treat Colorectal Cancer – Treatment Algorithm with Dr. Smitha Krishnamurthi

Oncology Brothers

Play Episode Listen Later Apr 20, 2026 25:08

In this episode of the Oncology Brothers podcast, we kicked off a three-part series on colorectal cancer, starting with the current treatment algorithm. They are joined by Dr. Smitha Krishnamurthi, a GI medical oncologist from the Cleveland Clinic, who walks through the evolving standard of care from early-stage disease all the way to refractory metastatic 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/ Key topics discussed included: • The evolving role of ctDNA as both a prognostic and predictive tool in stage two and three colon cancer, including its utility in oligometastatic disease surveillance. • Neoadjuvant versus adjuvant immunotherapy in MSI-high resectable colon cancer, comparing the NICHE-2 and ATOMIC trial approaches and when to use each. • Single-agent versus dual checkpoint inhibition with Nivo-Ipi for MSI-high metastatic disease, based on CHECKMATE-8HW data showing a PFS hazard ratio of 0.21. • Sequencing strategies in RAS-mutant and RAS wild-type metastatic colorectal cancer, including the role of sidedness, anti-EGFR therapy, and refractory options like fruquintinib, TAS-102, and regorafenib. Join us for this comprehensive discussion on colorectal cancer management in 2026. Don't forget to like, subscribe, and check out our other episodes for more insights on oncology! #ColorectalCancer, #MSIHigh, #BRAFV600E, #ctDNA, #GIOncology, #OncologyBrothers

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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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Localized Colorectal Cancer — Microlearning Activity 2: Proceedings from a Session Held Adjunct to the 2026 ASCO GI Cancers Symposium

Play Episode Listen Later Apr 13, 2026 15:06

Featuring perspectives from Dr Stacey A Cohen, Dr Christopher Lieu and Dr Jenny Seligmann, moderated by Dr Lieu, including the following topics: Adjuvant treatment planning for Stage II or III microsatellite instability-high colon cancer (0:00) Roles of circulating tumor DNA (ctDNA), POLE mutations and advanced age in adjuvant treatment planning (6:08) Role of ctDNA in adjuvant treatment planning for Stage III colon cancer (12:31) CME information and select publications

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Episode 492: Novel Biomarkers and Targets in Germ Cell Tumors

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Apr 6, 2026 33:25

This podcast features Dr. Mike Glover from MDACC discussing recent advances in germ cell tumor research, focusing on novel biomarkers like microRNA and ctDNA, and emerging therapies targeting Claudin-6. The conversation explores how these innovations could transform diagnosis, prognosis, and treatment strategies.

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How to Treat Bladder Cancer – Drs. Stephanie Berg (Medical Oncologist) & Joshua Meeks (Urologist)

Oncology Brothers

Play Episode Listen Later Apr 2, 2026 25:21

Welcome to the Oncology Brothers podcast! In this episode, we dived into the evolving treatment algorithms for bladder cancer following the latest data presented at GU ASCO 2026. 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 role of immunotherapy in non-muscle invasive bladder cancer, highlighting the recent positive trials: CREST with Sasanlimab and POTOMAC with Durvalumab. Insights on the current standard of care and the implications of combining BCG with immunotherapy. The shift in treatment strategies for muscle-invasive bladder cancer, including the new standard of care with the EV-Pembro combination and its impact on pathologic complete response rates. The challenges and considerations in managing side effects associated with new therapies, as well as the importance of patient selection and coordination between urologists and medical oncologists. The emerging role of ctDNA in guiding treatment decisions and the ongoing discussions around the sequencing of therapies in refractory settings. Hope you enjoy this informative discussion that aims to keep you up to date in the world of cancer treatment, here focusing on bladder cancer. Subscribe to our channel for more episodes and discussions on the latest in oncology! #BladderCancer, #NMIBC, #MIBC, #Immunotherapy, #GU26, #OncologyBrothers

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JCO Article Insights: ctDNA in DLBCL - Ready for Prime Time?

Play Episode Listen Later Mar 30, 2026 13:53

In this episode of JCO Article Insights, host Dr. Ash Gurumurthi summarizes JCO articles, "Phased Variant–Supported Circulating Tumor DNA as a Prognostic Biomarker After First-Line Treatment in Large B-Cell Lymphoma: Findings From the DIRECT Study" and " Prospective Validation of Circulating Tumor DNA Measurable Residual Disease After First-Line Therapy in Large B-Cell Lymphoma" TRANSCRIPT Ash Gurumurthi: Hi and welcome to JCO Article Insights. I'm your host, Ash Gurumurthi, and today we will be discussing two articles, both published in the Journal of Clinical Oncology, on the real-world utility of circulating tumor DNA (ctDNA) MRD in newly diagnosed large B-cell lymphoma. The first study is the article "Phased-Variant-Supported Circulating Tumor DNA as a Prognostic Biomarker After First-Line Treatment in Large B-Cell Lymphoma: Findings From the DIRECT Study" by Dr. Joanna Krupka and colleagues in the United Kingdom. For the sake of convenience, I'll refer to this as the DIRECT study. The second study is "The Prospective Validation of Circulating Tumor DNA Measurable Residual Disease After First-Line Therapy in Large B-Cell Lymphoma" by Dr. Steven Wang and colleagues in the Netherlands, referred to as the HOVON 902 study. By way of background, I wanted to talk about MRD in hematolymphoid malignancies. Nodal diseases have lacked a robust biomarker for end-of-treatment response. They have relied historically on PET scans interpreted using the semiquantitative Deauville 5-point scale, which has a high negative predictive value but a limited positive predictive value. The poor positive predictive value for survival results in extended follow-up with serial imaging for risk stratification with unnecessary and invasive biopsies. There have been recent revolutionary advancements in ctDNA MRD in B-cell lymphoma. The use of ctDNA in lymphoma began with CAPP-seq, which tracked single nucleotide variants that were tumor specific but was limited by excessive background sequencing noise with false negatives. To overcome this, Dr. Kurtz and colleagues developed the proprietary PhasED-seq assay. This tracks well-recognized phased mutations on the same DNA strand in cis configuration within hypermutated regions that are unique to B-cell lymphoma. Using this method, they pushed their limit of detection at 95%, the so-called LOD95, to 0.7 parts per million under optimal circumstances with 120 nanograms of input cell-free DNA from plasma. Based on the use of the PhasED-seq assay in trials of newly diagnosed large B-cell lymphoma with the use of investigational agents, the NCCN currently recommends consideration of ctDNA MRD assay with a detection limit of less than 1 part per million if biopsy is not feasible for a positive end-of-treatment PET. However, I believe this threshold needs reconsideration given it is based on an ideal assay LOD95 under optimal circumstances rather than sample-specific LOD95. Real-world validation of the role of end-of-treatment ctDNA and appropriate thresholds for sample-specific LOD95 were lacking until the publication of these two studies. The DIRECT and the HOVON 902 studies were multicenter, prospective trials using real-world cohorts of newly diagnosed large B-cell lymphoma treated with standard anthracycline immunochemotherapy, ie, R-CHOP chemotherapy. They validated end-of-treatment ctDNA MRD response measured on a phased-variant platform and found them to be strongly prognostic for relapse and survival. This was independent of PET imaging or baseline clinical prognostication like the International Prognostication Index, the IPI. They also demonstrated a threshold with an LOD95 of approximately 1 in 100,000 is necessary for clinical utility. Both trials recruited over a similar period between 2020 to 2023, with the DIRECT study conducted within the National Health Service in the United Kingdom and the HOVON 902 as a national study in the Netherlands. For survival analysis, only patients who reached the landmark event of end of treatment with an available ctDNA MRD sample without progressive disease or death at that time point were included. These studies evaluated similar-sized cohorts with 134 patients for HOVON 902 and 151 patients for the DIRECT study. As expected, their baseline demographics are reflective of a real-world population of newly diagnosed cases with large B-cell lymphoma. Although both used comparable statistical methodologies with time-to-event analysis, the primary outcomes vary, making headline comparisons quite challenging. The DIRECT study utilized the time to tumor progression, censoring death unrelated to disease. This was done to isolate the molecular impact of detectable ctDNA at the end of treatment. In contrast, the HOVON 902 study used progression-free survival, which counts all-cause mortality as an event. This naturally results in lower event-free rates for PFS compared to TTP in the DIRECT study. The trials differed in their choice of phased-variant platforms, with the DIRECT study developing an independent, fully open-source phased-variant ctDNA assay. This has been released on GitHub. In contrast, the HOVON 902 study utilized PhasED-seq by Foresight Diagnostics, which is currently the only proprietary and commercially available phased-variant assay for lymphoid malignancies. Interestingly, despite the differences in platforms and the primary end points, the results were remarkably consistent. The DIRECT study found a highly significant difference in the 2-year TTP rate of 96% in those with undetectable ctDNA MRD at the end of treatment compared to 45% in those with detectable ctDNA, with a hazard ratio of 15. Similarly, the HOVON 902 study found a significantly superior 3-year PFS of 85% in those with undetectable ctDNA compared to 17% with detectable ctDNA, with a hazard ratio of 10. Crucially, both studies found end-of-treatment ctDNA MRD significantly outperformed PET response assessment for long-term PFS. In fact, for the end point of PFS in both trials, the baseline IPI lost all statistical significance in both univariate and multivariable analysis when accounting for ctDNA MRD and PET status at the end of treatment. While both studies demonstrate the superiority of ctDNA MRD compared to PET in predicting survival, interestingly, the combination of both tests appeared to be complementary in identifying the highest-risk group. The HOVON 902 study identified 13 patients who were double positive, ie, they were positive with end-of-treatment PET and detectable ctDNA MRD. Every single one of these patients progressed over a 3-year period with a dismal overall survival of 17%. The DIRECT study mirrored these findings with the same double-positive group having a 2-year time to progression rate of 23%. Given consistency in identifying the poor outcome of this double-positive population in both studies, this is clearly a group that would benefit from trial-based approaches like consolidation or, alternatively, frequent surveillance for clinical relapse. On the other hand, the best-performing group was the double negative, ie, those who had achieved PET negative and ctDNA undetectable at the end of treatment. The double-negative group had a 2-year time to progression of 97% in the DIRECT study and a 3-year PFS of 88% in the HOVON 902 trial. This is quite impressive. Based on these findings, we can anticipate that ctDNA may complement rather than wholly replace PET at the end of treatment for response assessment. Perhaps the most critical finding from both studies challenged current NCCN-recommended ctDNA MRD sensitivity threshold of achieving less than one part per million. While phased-variant assays can theoretically detect this, this is under optimal conditions, specifically 120 nanograms of input cell-free DNA. In both trials, only 3% of samples could achieve this sensitivity, with the vast majority limited to a sample-specific LOD95 of approximately 1 in 100,000 informative reads. The primary constraint was simply limited plasma volume collected, a denominator problem of input cell-free DNA. For example, the HOVON 902 study had a median plasma volume of 5 mL, yielding 20 nanograms of input DNA. The DIRECT study elegantly demonstrated bridging the gap to attain the NCCN standard of LOD95 of less than 1 part per million is practically impossible. This would require greater input DNA, attained through a 20- to 30-milliliter collection of plasma rather than the standard 10 milliliters, and a massive 20- to 40-fold increase in sequencing depth. With the current real-world sensitivity of roughly 1 in 100,000 in both these studies, the negative predictive value is already nearly at 90%. There is going to be diminishing returns for further analytical sensitivity. This strongly suggests that the NCCN guidelines should be updated to prioritize achievable sample-specific LOD95 rather than assay-specific theoretical limits. Collectively, these studies validate the real-world utility of ctDNA MRD as an independent predictor of long-term outcomes following first-line therapy of large B-cell lymphoma. Finally, after two decades of the default R-CHOP for all, the field of aggressive large B-cell lymphoma is taking leaps and bounds by integrating ctDNA MRD with the current wave of bispecific and cellular therapies. I want to now leave you with my five key clinical takeaways from both these studies. ● Firstly, ctDNA MRD is a more potent independent predictor of outcome than end-of-treatment PET/CT and baseline IPI. ● Second, ctDNA MRD in first-line large B-cell lymphoma is already reshaping clinical trial space with therapeutic escalation and de-escalation strategies based on ctDNA kinetics during treatment, as well as identifying candidates with persistent ctDNA at the end of treatment for consolidation approaches. ● Thirdly, this technology is ready for prime time. Whether this is through Foresight's PhasED-seq assays or the open-source method released by the DIRECT group, academic centers can now operationalize this in routine clinical care. ● Fourth, biology clearly provides a ceiling. Current sensitivity goals of less than one part per million as recommended by the NCCN are limited by the actual amount of cell-free DNA we can extract from a patient's blood, not just the assay's technology. I believe these two studies will inform the NCCN's next revision to move away from theoretical assay limits to a more realistic sample-specific LOD95 of approximately 1 in 100,000. ● Finally, it appears that the end-of-treatment ctDNA MRD test may be complementary to PET/CT rather than a replacement. Clearly, the best outcomes are seen in double-negative patients, while double-positive results, ie, positive end-of-treatment PET and detectable ctDNA at the end of treatment, identify a group with an extremely high risk of early progression who may need early intervention. Thank you for listening to JCO Article Insights. Please come back for more interviews and article summaries, and be sure to leave us a rating and review so others can find our show. For more podcasts and episodes from ASCO, please visit asco.org/podcasts. 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.

S16 Ep33: Real-World Data Support ctDNA-Guided Treatment Strategies in FGFR2-Altered Cholangiocarcinoma: With Marina Baretti, MD

JCO Precision Oncology Conversations

Play Episode Listen Later Mar 25, 2026 19:41

Welcome to OncLive On Air®! I'm your host today, Ashling Wahner.OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.In today's episode, Marina Baretti, MD, discussed the real-world utilization of tissue-free circulating tumor DNA (ctDNA) monitoring in cholangiocarcinoma (CCA). Baretti is an assistant professor and the Jiasheng Chair in Hepato-Biliary Cancer Research at Johns Hopkins University School of Medicine, as well as co-director of the Liver and Biliary Cancer Multidisciplinary Clinic at the Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland. In the exclusive interview, Dr Baretti discussed multiple potential roles for ctDNA testing in CCA management, including the detection of minimal residual disease following curative-intent surgery, longitudinal monitoring of treatment response in advanced disease, and identification of emergent resistance mechanisms with targeted therapy.Baretti also reviewed findings from a small real-world observational analysis of 44 patients, in which a tissue-free ctDNA assay demonstrated high sensitivity, detecting variant allele frequencies as low as 0.2% and identifying actionable alterations in most patients; ctDNA dynamics also correlated with response and enabled early detection of resistance alterations, including secondary FGFR2 mutations, prior to radiographic progression in select cases.Lastly, Baretti contextualized these findings within the broader treatment landscape by reviewing data from the phase 2 FIGHT-202 trial (NCT02924376), which supported the FDA approval of pemigatinib (Pemazyre) in patients with previously treated CCA harboring FGFR2 fusions or rearrangements. Real-world data have confirmed the efficacy and safety of this agent observed in clinical trials, reinforcing the importance of comprehensive molecular profiling._____That's all we have for today! Thank you for listening to this episode of OncLive On Air. Check back throughout the week for exclusive interviews with leading experts in the oncology field.For more updates in oncology, be sure to visit www.OncLive.com and sign up for our e-newsletters.OncLive is also on social media. On X and BlueSky, follow us at @OncLive. On Facebook, like us at OncLive, and follow our OncLive page on LinkedIn.If you liked today's episode of OncLive On Air, please consider subscribing to our podcast on Apple Podcasts, Spotify, and many of your other favorite podcast platforms,* so you get a notification every time a new episode is posted. While you are there, please take a moment to rate us!Thanks again for listening to OncLive On Air.*OncLive On Air is available on: Apple Podcasts, Spotify, CastBox, Podcast Addict, Podchaser, RadioPublic, and TuneIn.This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.

JCO PO Article Insights: Analytical Validation of Tumor-Informed ctDNA Assays for MRD

Play Episode Listen Later Mar 25, 2026 11:28

In this JCO PO Article Insights episode, host Jordan Goldstein summarizes the article, "Generic Protocols for Analytical Validation of Tumor-Informed Circulating Tumor DNA Assays for Molecular Residual Disease: The Blood Profiling Atlas in Cancer's Molecular Residual Disease Analytical Validation Working Group Consensus Recommendation" by Baden et al. TRANSCRIPT

cancer validation informed tumors baden analytical assays ctdna

How “Cancer Poop” Is Changing Cancer Care | The Eye Believe Podcast

The Eye Believe Podcast

Play Episode Listen Later Mar 23, 2026 38:22 Transcription Available

In this episode of the Eye Believe Podcast, Danet sits down with Dr. Vincent Ma to discuss an emerging and exciting tool in cancer monitoring: ctDNA (circulating tumor DNA)—or as Dr. Ma memorably calls it, “cancer poop.” Dr. Ma breaks down this complex topic in a way that's easy to understand, explaining: What ctDNA is and how it works How it can be tested and monitored over time How he's using ctDNA in his practice to better track disease and guide care for his patients This conversation offers a unique look at how innovative science is becoming more accessible—and how tools like ctDNA may help improve early detection, monitoring, and personalized treatment strategies. Whether you're a patient, caregiver, or simply curious about the future of cancer care, this episode provides valuable insight into a rapidly evolving area of research. Tune in to learn how something as unexpected as “cancer poop” could play an important role in advancing cancer care.

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Bladder Cancer Breakthroughs: New NMIBC Therapies and EV + Pembrolizumab Updates From ASCO GU 2026

CCO Oncology Podcast

Play Episode Listen Later Mar 23, 2026 18:57

In this episode, Sam S. Chang, MD, MBA, and Matthew D. Galsky, MD, discuss the rapidly evolving treatment landscape in bladder cancer, highlighting new therapeutic options, emerging clinical trial data, including the latest results presented at ASCO GU 2026, and the growing role of biomarkers and multidisciplinary care, including: New treatment options for BCG-unresponsive non–muscle-invasive bladder cancer Intravesical therapies such as nadofaragene and N-803 The role of ctDNA in measurable residual disease detection Presenters: Sam S. Chang, MD, MBA Patricia and Rodes Hart Chair of Urologic Surgery Chief Surgical Officer Vanderbilt Ingram Cancer Center Nashville, Tennessee Matthew D. Galsky, MD Lillian and Howard Stratton Professor of Medicine Icahn School of Medicine at Mount Sinai Director, Genitourinary Medical Oncology Co-Leader, Cancer Clinical Investigation Program Associate Director for Translational Research Tisch Cancer Institute New York, New York Link to full program: https://bit.ly/479RgQn Get access to all of our new podcasts by subscribing to the Decera Clinical Education Oncology Podcast on Apple Podcasts, YouTube Music, or Spotify. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

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S16 Ep31: ctDNA Testing At Progression May Help Detect Resistance and Guide Sequencing in GIST: With Drs Jonathan Trent, MD, PhD, and Neeta Somaiah, MD

Play Episode Listen Later Mar 20, 2026 26:26

In today's episode of OncLive On Air®, Jonathan Trent, MD, PhD, and Neeta Somaiah, MD, sat down to discuss the evolving role of circulating tumor DNA (ctDNA) testing in gastrointestinal stromal tumors (GIST), as well as the importance of identifying both initial drivers of disease and secondary resistance mechanisms when approaching frontline treatment selection and overall therapeutic sequencing.Trent is a professor of medicine, associate director of Clinical Research, and director of the Sarcoma Medical Research Program at the University of Miami Miller School of Medicine, in Florida. Somaiah is a professor and chair of the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.Drs Trent and Somaiah began their discussion by highlighting the rarity of GIST, underscoring the importance of evaluation at specialized sarcoma centers and comprehensive molecular testing to identify driver alterations.Somaiah then reviewed the molecular landscape of GIST, noting that approximately 70% to 80% of tumors harbor activating mutations in the KIT gene, while additional cases involve rarer alterations such as BRAF or NTRK fusions. Of note, resistance to imatinib (Gleevec) frequently emerges through secondary mutations in KIT exons 13 or 17, which can influence sensitivity to subsequent TKIs.ctDNA testing may help detect these resistance mechanisms, particularly at progression or when tissue is limited, enabling clinicians to refine sequencing strategies, both experts explained. They also discussed how mutation-informed approaches may guide treatment selection, including emerging strategies such as combining sunitinib (Sutent) with bezuclastinib to address resistant clones involving KIT exon 13 or 17 alterations.This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.

university guide phd medicine testing md resistance progression detect md phd clinical research gist sequencing miami miller school neeta texas md anderson cancer center braf ctdna tkis gleevec onclive sutent

Navigating Therapeutic Advances in EGFR-Mutated NSCLC

ASCO Daily News

Play Episode Listen Later Mar 19, 2026 19:24

Dr. Monty Pal and Dr. Vamsi Velcheti discuss the evolving treatment landscape in EGFR-mutated non-small cell lung cancer, including landmark trials like FLAURA2, novel drug therapies, and the growing importance of ctDNA and MRD testing. TRANSCRIPT Dr. Monty Pal: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. Monty Pal. I'm a medical oncologist and professor and vice chair of academic affairs at the City of Hope Comprehensive Cancer Center in Los Angeles. Today, I'm truly delighted to introduce Dr. Vamsi Velcheti, who's a professor of medicine and the chief of hematology-oncology at the Mayo Clinic in Jacksonville, Florida. We'll be discussing the expanding treatment landscape in EGFR-positive lung cancer and how to navigate the challenges of balancing treatment efficacy, toxicity, and patient quality of life in the EGFR-positive space. Just FYI, our full disclosures are available in the transcript of this episode. Vamsi, it's so great to have you on the podcast. Thank you so much for being here. Dr. Vamsi Velcheti: Thank you, Monty. It's a pleasure to be here with you. It's a really exciting topic and there are a lot of updates in the EGFR space. Dr. Monty Pal: So, I'm going to need your help with this because I'll be honest with you, I see very little lung cancer, if any, in my practice. I'm pretty much exclusively kidney cancer these days. I'm coming on 20 years at City of Hope now, and I still remember when trials like ECOG 1599 were presented with, you know, platinum doublets. And, of course, the field has changed a lot since then. But tell us a little bit about the first-line landscape, and I think just for the sake of time, we're going to stick with EGFR-positive disease here. What does it look like these days? Dr. Vamsi Velcheti: Monty, the foundation of care remains the third-generation EGFR inhibitors. These are selective EGFR inhibitors, like osimertinib. We've had an evolution of the development of these TKIs. Like, you know, we had the first-generation, second-generation, not-so-selective EGFR inhibitors. Now we have mutant-selective EGFR inhibitors in the clinic, and they're doing a really good job. And these are quite effective in patients who have classical activating mutations. But the reality is that these have not been transformative. These agents have fundamentally changed the response patterns, excellent CNS penetration, and very good tolerability profile. However, we don't see a lot of durability in terms of the response. So, what's different today is now there have been several trials in combination with these third-generation EGFR inhibitors that have really laid the foundation of how we kind of think about EGFR-positive disease. At the high level, there are a lot of challenges to selecting the patients for these combination-based modalities. I'm assuming we'll be talking more about these different trials and different approaches. Some of these combination-based strategies have really moved the needle in terms of improving overall survival and really improving long-term outcomes and durability in our patients. Dr. Monty Pal: And we are going to get into the weeds on this in just a moment. But I did kick off this podcast talking about chemotherapy, ECOG 1599. It does seem as though chemotherapy is still a component of management in advanced non-small cell lung cancer. So, can you tell us about, perhaps first, you mentioned osimertinib, you know, some of these next-generation EGFR inhibitors. Tell us about the role of chemo plus osimertinib. Dr. Vamsi Velcheti: That's exactly where I was going with the combination-based strategies. You know, we first started off with our earlier trials in the EGFR space evaluating the question of, are targeted therapies, are these highly effective, third-generation, EGFR-selective inhibitors, superior to platinum-doublet chemotherapy? And we've had multiple trials demonstrating that, like the FLAURA trial and in the past with second-generation EGFR inhibitors like erlotinib and gefitinib and afatinib. So, we know that these TKIs actually perform better than platinum-doublet chemotherapy. Now, we have a large, global, phase 3 trial data from the FLAURA2 trial, which looks at the question, "Hey, you know, osimertinib is better than chemotherapy, platinum-doublet chemotherapy. Can we do even better by combining osimertinib with platinum-doublet chemotherapy?" So, FLAURA2 answered that question. This is a large, phase 3 trial, and it's a positive trial with improved durability of disease control and improving overall survival with combination with chemotherapy. So, it's a very important and landmark trial, and essentially combining osimertinib with a platinum-based chemotherapy improved responses, deepened responses, and improved overall survival and really changing the disease trajectory. And this strategy is definitely compelling, especially in patients who have certain clinical high-risk features like, you know, patients who have high disease burden or patients who are sometimes having rapid disease progression early on osimertinib, especially with patients who have a lot of visceral disease burden. So, intensifying treatments up front could alter the natural trajectory of the disease. Dr. Monty Pal: So, you sort of alluded to this in that last part there, but is that kind of how you in clinical practice select? Is it based on, you know, visceral involvement? Is it based on rapidity of disease where you think about adding chemotherapy to osimertinib? Maybe you can give us the corollary. Which patients do you just use osimertinib alone in, for instance? Dr. Vamsi Velcheti: Definitely, there are some patients who have low disease burden and they have the classical mutations, like an exon 19 deletion. And these patients, especially if they don't have a lot of disease burden, they don't have CNS involvement, there may be a subset of patients who could just do fine on osimertinib of course, with close monitoring of the disease. I guess we'll get into that later, how do we do that with either ctDNA or like closer imaging or both. So, there may be some opportunity to kind of escalate patients' treatments based on certain clinical characteristics or radiographic characteristics or certain biological characteristics informed by ctDNA or other approaches. Dr. Monty Pal: No, that's interesting. And you're right, we will chat about ctDNA in just a bit. But before we get there, I think one of the big agents that has really sort of come to the fore in advanced non-small cell lung cancer is amivantamab. I've heard a lot about this in the context of even kidney cancer because in certain subsets, I'm interested in MET-directed therapies and so forth, right? So maybe tell us a little bit about the mechanism of amivantamab first, and then maybe tell us about this pivotal MARIPOSA trial where it's combined with lazertinib. Dr. Vamsi Velcheti: So, the MARIPOSA trial compared lazertinib alone with amivantamab plus lazertinib. And this trial demonstrated overall survival advantage, and there were key differences in terms of tolerability and the safety of amivantamab, which is an EGFR and MET bispecific, and there were certain kind of unique toxicity profiles that make it a little different than the intensification approach with chemotherapy through the FLAURA2 trial. So, there's a trade-off in terms of the toxicity profile. It's a different agent and a different management protocol in terms of dermatological toxicity management that clinicians need to be comfortable with. And also, there are certain unique issues in terms of amivantamab; there's a higher rate of infusion-related reactions, there's an increased risk for edema and VTEs because of amivantamab. Certainly a different toxicity profile, different management paradigm there in terms of longitudinal care of these patients requiring dermatological care and like, you know, close monitoring and prophylaxis VTEs. But having said that, definitely it's a different strategy, and it kind of changes the biology and the natural history of the cancers, and we do see some durability of responses that we see with the MARIPOSA. So, it's certainly a great alternative, at least for some patients. Dr. Monty Pal: That was a great overview of MARIPOSA. Now comes the really difficult question, which is, how do you choose between the two? You have these two great options, right, for EGFR-positive patients. You've already highlighted some of the distinctions in terms of toxicity. I think the audience is well aware of the side effects of chemo-doublet, perhaps even the EGFR-based therapies. Amivantamab is quite new. Give us a sense of how you in clinical practice decide between the two potential options here. Dr. Vamsi Velcheti: Yeah, I think that's the big challenge. I think these are two independent strategies that have evolved through the phase 3, and both of them have demonstrated overall survival benefit. So, the way I think about this is in three dimensions, right? Like, the disease biology, the patient priorities, and feasibility of care delivery. So, when I talk about the disease biology, you know, the mechanism is very different, and MET is a very dominant driver of disease in EGFR-altered patients and it's a significant mechanism of resistance, acquired resistance to TKIs. So, certainly I think there's a patient population that could benefit from a MET-directed therapy up front. However, we don't have great data to kind of really demonstrate how using amivantamab in the front line is going to change that. And are there like perhaps like some patients who we could identify who would benefit from such a strategy? Very recently, there have been some approvals in the second-line setting in lung cancer, not in the EGFR space, but like in generally in lung cancer, with the MET ADCs, and those drugs are approved with a companion diagnostic, which requires MET IHC testing. So, what has happened, at least in large academic practices and also I think in the community now, they have been checking for MET IHC expression more routinely in lung cancer. What we have been doing in our institution is we have been doing MET IHC as a reflex for all patients with EGFR, not just EGFR, but all non-small cell lung cancer patients. What that has done is now, like, we have been increasingly testing patients with EGFR for MET. And there's clearly a subset of patients who have de novo MET expression and a high MET expression. And those patients, I've been kind of like preferentially treating them with the MARIPOSA regimen. But again, I have to caution the audience that we still don't have data that MET IHC is going to help us make those decisions, whether it's better than like a FLAURA2 regimen. But however, in the second-line setting in the CHRYSALIS trial, we know that MET is a very powerful predictor of response to amivantamab. We really need more data there, but that's what I have been doing in my practice. But also, there's a lot of patient preference here. Like, there are some patients who don't want chemotherapy, and they want a non-chemotherapy approach. So, certainly there are some patients who prefer to have amivantamab. And now with the amivantamab, the subcutaneous version, the infusion reactions and the logistics of actual administration of amivantamab are more favorable with the subcutaneous approval. So, those are some of the elements that we need to take into account. Dr. Monty Pal: Well, I want to hone in on that because this subcutaneous administration route has been a big debate that I've seen on social media. Tell us, how much easier does it actually make the amivantamab experience? Does it cut down on the rash? Is it just infusion reactions? What's been your clinical experience? Vamsi Velcheti, MD: So, the subcutaneous administration of amivantamab has definitely improved the infusion reaction issue. Very rarely patients have infusion reaction now with the subcutaneous injections. And also, the infusion time is much, much shorter. Like we don't need a lot of infusion time, which is sometimes a challenge in busy infusion clinics. We need to take that into account. As far as the impact of the subcutaneous formulation on dermatological toxicity, we haven't really seen significant difference in terms of the intensity or rates of dermatological toxicity with subcutaneous. The benefits are really with the infusion reaction, the ease of administration. And interestingly, in the PALOMA trial, it also seems to be, even though this was not the primary endpoint of the study, there seems to be some suggestion that the subcutaneous amivantamab seems to have improved OS compared to the IV amivantamab. We don't really understand why, but that's a finding from the trial that's very intriguing. Dr. Monty Pal: That is really fascinating. I'm kind of curious to see how that's going to pan out. I'm going to shift gears a little bit here. And, you know, as we sort of close, I wanted to talk a little bit about biomarkers. I mean, this is obviously not a lung cancer-specific issue. It's something we think about across the board. But what I will say is that there are certain commonalities, and in bladder cancer, we think a lot now about ctDNA. But you've been way ahead of the game in lung cancer. Tell us how you guys use ctDNA, maybe both from the standpoint of monitoring for mutational status, but if you can, maybe offer some insights into some of these new MRD tests that are available too. Dr. Vamsi Velcheti: Yeah, it's rapidly evolving. Certainly, I think in the lung cancer space, you know, this has really kicked off in the lung cancer space with incorporating ctDNA into the workflow. Of course, you know, like baseline evaluation, we still kind of heavily rely on tissue genomic sequencing. But as you know, with targeted therapy, a lot of these patients have disease that evolves over time, and changes in terms of mutational pattern driving acquired resistance is a major issue across different molecular subtypes. And especially so in EGFR, when there are certain actionable opportunities associated with that transformation. So, we need to kind of have like a longitudinal snapshot of how we monitor these patients. So, the ctDNA has come to be like a tool that has now come to the forefront of clinical workflow, and almost all my patients who are having disease progression have ctDNA for kind of evaluating for resistance and informing treatment decisions, especially in EGFR. But having said that, there are a lot of challenges in terms of using ctDNA as a tool for monitoring. There are a lot of different types of assays and different platforms, and being able to use this as a quantitative tool that would be used along with the CT scans that we routinely use in clinical practice has been a challenge. And I think I would love to hear your perspectives as well, Monty, about how you're thinking about that in bladder and other disease contexts. But having said that, I think there's a lot of opportunity to incorporate ctDNA and MRD assays into clinical decision-making. Right now, in terms of clinical trials and clinical development, there have been some very interesting trials that are currently ongoing, especially in the EGFR space. We know that patients who clear ctDNA, based on some retrospective data and also like some retrospective-prospective data from trials that have already read out, that patients who clear ctDNA early with target therapy tend to do much better. They have a longer durability of response. There may be a subset of patients who have, even though they're having radiographic response, they have persistent ctDNA after a certain time point of initiation of targeted therapy. Those patients may require escalation of therapy. We don't yet know. I can't recommend that as a standard right now because we don't have clinical evidence to support that. But however, some of the clinical trials, like the ELIOS trial that's being done right now, that's actually completed enrollment, we'll hopefully see the results very soon. So, there is an emerging thought that instead of intensifying treatment for all patients with EGFR, there may be a population that may be just fine with frontline osimertinib monotherapy and introducing the intensification strategy at the time of emergence of MRD or progression on ctDNA before radiographic progression. So, there are a lot of adaptive molecular response criteria that we are kind of exploring in clinical trials that could inform how the future is going to look like for EGFR and other perhaps targeted therapies as well. So, it's fascinating, and I think there's a lot of opportunity there. Dr. Monty Pal: You know, you asked for my perspective. I actually think that what you highlighted there is the most interesting opportunity for ctDNA: the ability to de-escalate therapy. In terms of drug development, we've done so much to bring new therapies to patients, and now it's a bit of an embarrassment of riches, but the downside is that I feel like we tend to overtreat a lot of patients in the clinic. So, I definitely view MRD, you know, some of these other ctDNA techniques with methylation and so forth that may not be sort of tumor-dependent or bespoke could be incredibly, incredibly helpful. You touched on sort of the future, right, in this last section here with biomarkers. But give us a sense now in terms of novel drug therapies in the EGFR space. What are you most excited about moving forward in 2026 and beyond? Dr. Vamsi Velcheti: Yeah, I think there's a lot going on in this space, and not just this space, but across lung cancer and others as well. Like looking at the next generation of targets for ADCs. And I think a lot of these have to do with…so far in the drug development space, as you know, the improvements in clinical outcomes has been very incremental. So, we really need to make that big leap. And I think the big leap is not going to come from, in my opinion, from the next ADC, but it's going to come from how we tailor treatments and how we monitor disease better and how do we kind of incorporate the next treatment earlier and not wait for the radiographic progression. So, there's a lot of opportunity there to integrate biomarkers and dynamic biomarkers into clinical trial design and incorporating the recent advances in terms of drug design. You know, we have a lot of assets in the EGFR space, the next-generation EGFR inhibitors that are kind of designed with resistance in mind and rational combination, knowing when to introduce those combinations is also equally important. So, there's a lot going on, really exciting times to be in drug development. The one thing that I really hope will come to the forefront in drug development, not just for lung cancer, but all disease groups, is to kind of really be thoughtful about how we incorporate these really cool molecular monitoring tools and creating a composite score with imaging to be able to like really design the next generation of clinical trials. Dr. Monty Pal: You're so spot-on with that. I definitely think that we're getting to this point where, you know, we could think about the next BiTE, the next CAR-T, the next ADC. But, you know, maybe it's time for us to start really honing in on appropriate applications of these drugs, honing in on the right dose and what have you, because I definitely see some issues there. Vamsi, this has just been terrific. I really want to thank you so much for sharing your fantastic insights with us today on the ASCO Daily News Podcast, and I really appreciate all your efforts to move the field of lung cancer forward. Dr. Vamsi Velcheti: Thanks, Monty. I really enjoyed the conversation. Dr. Monty Pal: Yeah, this was terrific. And thanks to our listeners as well. If you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:    Dr. Monty Pal  @montypal  Dr. Vamsi Velcheti @VamsiVelcheti Follow ASCO on social media:         ASCO on X   ASCO on Bluesky        ASCO on Facebook         ASCO on LinkedIn         Disclosures:      Dr. Monty Pal:     Speakers' Bureau: MJH Life Sciences, IntrisiQ, Peerview    Research Funding (Inst.): Exelixis, Merck, Osel, Genentech, Crispr Therapeutics, Adicet Bio, ArsenalBio, Xencor, Miyarsian Pharmaceutical    Travel, Accommodations, Expenses: Crispr Therapeutics, Ipsen, Exelixis   Dr. Vamsi Velcheti:  Honoraria: Galvanize Therapeutics Consulting or Advisory Role: Bristol-Myers Squibb, Merck, AstraZeneca/MedImmune, GSK, Amgen, Taiho Oncology, Novocure, Regeneron, Takeda, Janssen Oncology, Picture Health Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline

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Episodio 483: ASCO GU 2026 - KEYNOTE B15: EVP neoadyuvante vs Gem/Cis en cáncer de vejiga músculo-invasivo cisplatino elegible

Play Episode Listen Later Mar 10, 2026 42:19

En este episodio, Brian, Tom y Matt Galsky analizan los datos del estudio B15 sobre terapia neoadyuvante para el cáncer de vejiga músculo-invasivo cisplatino-elegible, centrándose en la eficacia de EV-Pembro en comparación con cisplatino-gemcitabina. Exploran la SLE, SG y las implicaciones de la duración del tratamiento así como su individualización. La conversación también aborda el papel del ctDNA en las decisiones terapéuticas, las histologías alternativas y la importancia de la terapia sistémica neoadyuvante. El episodio concluye con reflexiones sobre las futuras direcciones en el tratamiento del cáncer de vejiga y la relevancia de los estudios en curso.

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Oncology Nursing Update: Colorectal Cancer — An Interview with Dr Christopher Lieu on Molecular Residual Disease Analysis

Play Episode Listen Later Mar 6, 2026 59:00

Featuring an interview with Dr Christopher Lieu, including the following topics: Historical approach to the adjuvant treatment of localized colorectal cancer (CRC) (0:00) Perspectives on earlier-onset colorectal cancer and potential drivers; management of oligometastatic disease (13:16) Overview of cell-free DNA (circulating tumor DNA [ctDNA]) and techniques for its measurement (17:03) Reliability and prognostic capability of ctDNA as a biomarker for clinical status in patients with localized colorectal cancer (21:10) ctDNA assessment and treatment decision-making for patients with Stage II colon cancer (26:38) Potential incorporation of ctDNA assays into the management of metastatic colorectal cancer or microsatellite instability-high disease (34:29) Available clinical data with ctDNA assessment in localized rectal cancer (38:54) Current practice patterns with ctDNA assays for patients with localized colorectal cancer (41:17) Case: A woman in her early 40s with resected lower risk Stage III colon cancer requests ctDNA testing (45:47) Case: A man in his early 50s with Stage IIIB colon cancer wants to avoid adjuvant chemotherapy (50:39) Case: A man in his early 60s with Stage IV colon cancer receives a positive postoperative ctDNA assessment result (53:24) NCPD information and select publications

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Episode 486: ctDNA and utDNA Data in Peri-operative Urothelial cancer

data cancer operative summarythis ctdna

Play Episode Listen Later Mar 4, 2026 45:32

summaryThis episode explores the latest advances in circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) in bladder cancer management. Experts discuss how these biomarkers are transforming perioperative decision-making, prognosis, and personalized treatment strategies.

Episode 483: ASCO GU 2026 - KEYNOTE B15: Neoadjuvant EVP vs Gem/Cis in Cis-eligible MIBC