Evolving Strategies in Upper GI Cancer Ep 02.

In the second episode of The Gut-Onc Collab, Drs. Nicholas Hornstein, Timothy Brown, and Udhayvir Grewal tackle the explosive growth of targeted therapies in the Upper GI space. The team dives deep into the "how" and "when" of treating HER2-positive and HER2-negative gastric and gastroesophageal junction (GEJ) adenocarcinomas, moving from perioperative care to the second-line setting.   Key Takeaways: The Matterhorn Trial: Why adding Durvalumab to perioperative FLOT is an immediate practice-changer for resectable gastric/GEJ cancer, and the team’s "oncologist vs. purist" debate on extrapolating this to esophageal patients. Destiny-Gastric 04 (DG04): A look at Trastuzumab Deruxtecan (T-DXd) displacing the long-standing "Ram-Pac" regimen in the second line. The hosts share raw clinical experiences with its toxicity profile and why it is not "Trastuzumab 2.0." Horizon-GEA 01 & Zanidatamab: Analyzing the bispecific antibody that broke the 2-year median OS barrier. The team critiques the trial’s controversial control arm while acknowledging the undeniable "ball don't lie" efficacy data. Clinical Pearls: The necessity of repeat biopsies, the rise of liquid biopsy in monitoring HER2 status, and the "loperamide trick" for managing zanidatamab-induced diarrhea. From precision oncology to "triple-prophylaxis" anti-emetic strategies, this episode provides a roadmap for the modern management of Upper GI malignancies.   Chapters: (00:00) Matterhorn Trial Overview (05:38) Results and Impact (10:29) How Long to Treat (15:25) TDXd vs RamPac Results (16:05) TDXd Toxicity and Dosing (20:28) Liquid Biopsy Questions (21:16) Horizon GEA01 Setup (26:07) Results That Shift Care (32:58) Infusion Reaction Basics (35:17) Closing Reflections