OncLive® On Air

Two Onc Docs, hosted by Samantha A. Armstrong, MD, and Karine Tawagi, MD, is a podcast dedicated to providing current and future oncologists and hematologists with the knowledge they need to ace their boards and deliver quality patient care. Dr Armstrong is a hematologist/oncologist and assistant professor of clinical medicine at Indiana University Health in Indianapolis. Dr Tawagi is a hematologist/oncologist and assistant professor of clinical medicine at the University of Illinois in Chicago. In this episode, OncLive On Air® partnered with Two Onc Docs to bring a discussion of key data from the phase 3 MATTERHORN trial (NCT04592913), which were presented at the 2025 ASCO Annual Meeting. MATTERHORN was a randomized, double-blind, multinational study evaluating the addition of durvalumab (Imfinzi) to FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) in patients with previously untreated, resectable gastric or gastroesophageal junction adenocarcinoma. In the MATTERHORN trial, 948 patients were randomly assigned 1:1 to receive either durvalumab or placebo in combination with perioperative FLOT, followed by 10 cycles of durvalumab or placebo as adjuvant therapy. The primary end point was event-free survival (EFS); secondary end points included overall survival (OS) and pathological complete response (pCR). The trial met its primary end point. Durvalumab plus FLOT (n = 474) significantly improved EFS vs placebo plus FLOT (n = 474; HR, 0.71; 95% CI, 0.58-0.86; P < .001), representing a 29% reduction in risk of progression, recurrence, or death. The interim OS analysis showed a nonsignificant trend favoring durvalumab (HR, 0.78; 95% CI, 0.62-0.97; P = .025). The pCR rate was 19% (95% CI, 15.75%-23.04%) with durvalumab vs 7.2% (95% CI, 5.02%-9.88%) with placebo. Toxicity profiles were comparable between the 2 groups, though immune-related adverse effects were more frequent with durvalumab. Importantly, the addition of durvalumab did not delay surgery or initiation of adjuvant therapy. Although the MATTERHORN regimen is not yet FDA approved or included in the National Comprehensive Cancer Network guidelines, this trial demonstrates a promising EFS benefit and potential practice-changing implications, pending mature OS data and further molecular subgroup analyses, according to Armstrong and Tawagi.

In today’s episode, supported by Bayer, we had the pleasure of speaking with Alicia Morgans, MD, MPH, and Neal Shore, MD, FACS, about the FDA approval of darolutamide (Nubeqa) plus androgen deprivation therapy for patients with metastatic castration-sensitive prostate cancer (mCSPC). Morgans is the medical director of the survivorship program at Dana-Farber Cancer Institute; as well as an associate professor of medicine at Harvard Medical School, both in Boston, Massachusetts. Shore is the medical director of the Carolina Urologic Research Center. In our exclusive interview, Drs Morgans and Shore discussed the significance of this approval; key efficacy, safety, and quality of life data from the pivotal phase 3 ARANOTE trial (NCT04736199); and how this regulatory decision both opens doors for the treatment of more patients and raises questions about the optimal role of darolutamide in the management of mCSPC. 

In this episode of MedNews Week's Oncology Unplugged, host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was rejoined by Midhun Malla, MD, of the University of Alabama at Birmingham, to discuss therapeutic options for patients with metastatic colorectal cancer (mCRC), particularly in the third-line setting and beyond. In the final part of this 3-part episode miniseries, Drs Park and Malla explored the challenges faced by community oncologists, especially in rural or underserved areas, in accessing clinical trials, which remain a preferred disease management approach due to their role in advancing novel therapies. However, in the absence of trial availability or when patients are ineligible, they emphasized the importance of evidence-based, FDA-approved agents for later lines of therapy. Three primary agents were discussed for patients who have progressed on first-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) and second-line FOLFIRI (folinic acid, fluorouracil, and irinotecan) regimens: trifluridine/tipiracil (TAS-102; Lonsurf) plus bevacizumab (Avastin); fruquintinib (Fruzaqla); and regorafenib (Stivarga). These agents offer viable treatment pathways in biomarker-unselected patient populations. However, direct comparisons between these agents are lacking, as most were tested against placebo controls. The choice among them is often individualized based on patient performance status, prior exposure to biologics, and toxicity profiles. TAS-102 plus bevacizumab has generated promising results, though real-world data may show diminished efficacy due to frequent prior exposure to 5-fluorouracil and bevacizumab in US patients. Fruquintinib offers a VEGF-targeted approach with a more favorable hematologic toxicity profile, whereas regorafenib is associated with notable adverse effects, including hypertension, gastrointestinal toxicity, and mucositis. Park and Malla emphasized the importance of treatment sequencing, toxicity management, and individualized patient-centered care, including consideration of dose modifications to preserve quality of life in later-line settings. In addition to later-line options, the conversation also touched on emerging frontline therapies. Notable investigational agents include zanidatimab-hrii (Ziihera) and KRAS G12C–directed therapies. Additionally, a novel integrin-targeted cytotoxin is currently under evaluation at the University of Alabama at Birmingham in patients with treatment-naive mCRC. This agent induces apoptosis via caspase-8 activation and has demonstrated encouraging preclinical activity. Overall, the discussion highlighted a nuanced, biomarker-informed, and patient-tailored approach to mCRC management, emphasizing both the value of clinical trials and the importance of optimizing currently available therapies.

In today’s episode, supported by Immatics, we had the pleasure of speaking with Justin Moser, MD, about the ongoing phase 3 SUPRAME trial investigating the PRAME-directed T-cell receptor T-cell therapy IMA203 vs treatment of physician's choice in patients with previously treated, unresectable or metastatic cutaneous melanoma. Dr Moser is an associate clinical investigator, a melanoma and cutaneous oncology specialist, and a phase 1 trialist at HonorHealth Research Institute in Scottsdale, Arizona; as well as a research associate professor at the Arizona State University School of Medicine and Advanced Medical Engineering. In our exclusive interview, Dr Moser discussed the unique mechanism of action of IMA203, previously reported phase 1 data with this agent in patients with melanoma, and the design and potential future implications of SUPRAME. 

In this episode of MedNews Week's Oncology Unplugged, host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was rejoined by Midhun Malla, MD, a gastrointestinal oncologist at Allegheny Health Network in Pittsburgh, Pennsylvania, to discuss treatment personalization in metastatic colorectal cancer (mCRC), with a focus on BRAF V600E–mutant tumors, HER2-altered disease, and the clinical implications of tumor sidedness.

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

In this episode, OncLive On Air® partnered with Two Onc Docs to bring discussion of data from the phase 3 SERENA-6 trial (NCT04964934), which were presented at the 2025 ASCO Annual Meeting. SERENA-6 evaluated switching to camizestrant plus a CDK4/6 inhibitor vs continuing with a standard-of-care aromatase inhibitor plus a CDK4/6 inhibitor in the frontline setting in patients with hormone receptor–positive, HER2-negative advanced breast cancer whose tumors harbor an emergent ESR1 mutation. Drs Armstrong and Tawagi highlighted key efficacy, safety, and patient-reported outcomes from the study. They also noted the clinical implications of these findings, including how they might be currently applicable to clinical practice, as well as limitations of the research that warrant further investigation. 

In today’s episode, supported by Coherus BioSciences, we had the pleasure of speaking with Michael Dennis, MD, about recent updates to the nasopharyngeal carcinoma treatment paradigm. Dr Dennis is a physician at Dana-Farber Cancer Institute; as well as an instructor in medicine at Harvard Medical School, both in Boston, Massachusetts. In our exclusive interview, Dr Dennis discussed the latest National Comprehensive Cancer Center guideline updates for the treatment of patients with nasopharyngeal carcinoma; practice-informing data from the phase 3 JUPITER-02 trial (NCT03581786), which investigated first-line toripalimab-tpzi (Loqtorzi) plus chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma; and ongoing developments in the locally advanced treatment setting.

In today’s episode, we had the pleasure of speaking with Alexey Danilov, MD, PhD, about current challenges and emerging treatment approaches for the management of leukemia and lymphoma that were published in a manuscript based on proceedings from the inaugural Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma Conference. Dr Danilov is the Marianne and Gerhard Pinkus Professor of Early Clinical Therapeutics, medical director of the Early Phase Therapeutics Program for the Systems Clinical Trials Office, co-director of the Toni Stephenson Lymphoma Center, and a professor in the Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California. In our exclusive interview, Dr Danilov highlighted recent advances and controversies in the treatment of select patients with hematologic malignancies. He noted chemotherapy-free regimens that are shifting treatment paradigms in mantle cell lymphoma, preferred and emerging BTK inhibitors for the management of chronic lymphocytic leukemia, and the evolution of CD19-directed CAR T-cell therapies for diffuse large B-cell lymphoma. Dr Danilov concluded by taking a forward glance at future developments like BTK degraders and novel CAR T-cell therapy targets.

Episode Description In this podcast, expert Hope Rugo, MD, discusses her approach to treating patients with hormone receptor–positive/HER2-negative breast cancer from the early-stage to metastatic disease. Consideration of these complex clinical scenarios taken from tumor board discussions at the 42nd Annual Miami Breast Cancer Conference® highlight evolving strategies in breast cancer care and clinical decision-making. Acknowledgment of Educational Grant Support This activity is supported by educational grants from Exact Sciences Corporation; Lilly; Merck & Co, Inc; Novartis; PreludeDx; Puma Biotechnology, Inc; and Varian Medical Systems, Inc. Today’s faculty is: Hope S. Rugo, MD, FASCO Director, Women’s Cancers Program Division Chief, Breast Medical Oncology Professor, Department of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte, CA Professor Emeritus, UCSF Disclosures: Grant/Research Support: Ambrx; AstraZeneca; Daiichi Sankyo, Inc; F. Hoffmann-La Roche AG/Genentech, Inc; Gilead Sciences, Inc; Lilly; Merck & Co, Inc; Novartis Pharmaceuticals Corporation; OBI Pharma; Pfizer; Stemline Therapeutics. Consultant: Napo Therapeutics; Puma Biotechnology; Sanofi. Honoraria: Chugai; Mylan/Viatris. The staff of Physicians’ Education Resource®, LLC, have no relevant financial relationships with ineligible companies.  PER® mitigated all COI for faculty, staff, and planners prior to the start of this activity by using a multistep process. Off-Label Disclosure and Disclaimer This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this accredited activity is for continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any company that provided commercial support for this activity. Release Date June 20, 2025 Expiration Date June 20, 2026