MATTERHORN Trial Design and DFLOT Adoption: Integrating Immunotherapy Into Perioperative Practice

This segment centers on the MATTERHORN trial and its implications for future perioperative standards in resectable gastric and gastroesophageal junction adenocarcinoma. The panel reviews the study design, in which durvalumab was combined with FLOT in both the neoadjuvant and adjuvant settings, followed by up to one year of durvalumab maintenance, and event-free survival was the primary endpoint. They discuss why the schema, splitting chemotherapy before and after surgery while layering immunotherapy across the perioperative continuum, is viewed as clinically logical and consistent with prior FLOT-based trials. The conversation highlights questions that remain, including how ctDNA and biomarker analyses (such as PD-L1, MSI/MMR, HER2, and CLDN18.2) may help refine patient selection and interpret differential benefit across biologically distinct gastric cancer subtypes. The panel then considers real-world implementation issues if DFLOT becomes a standard option, including coordination between surgeons and medical oncologists, payer authorization, multidisciplinary workflows, prehabilitation, and the need for vigilance around overlapping toxicities when immunotherapy is added to FLOT.