Ep. 4: Next-Line Strategies and Practice Insights for Durvalumab in Gastric and GEJ Cancer
Key Points
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Progression after perioperative immunotherapy signals aggressive disease and highlights the importance of biomarker-driven therapy.
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FDA approval based on an intent-to-treat population allows treatment for all-comers, regardless of PD-L1 status.
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Multidisciplinary discussions and patient-centered decisions are key for sequencing therapy and managing adverse effects.
Managing Progression After Perioperative Immunotherapy
To close the discussion on gastric cancer held at an event coinciding with the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, discussed clinical approaches after disease progression on perioperative durvalumab with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT). They were joined by panelists Angela Alistar, MD, of Atlantic Health; Steven Maron, MD, MSc, of Memorial Sloan Kettering Cancer Center; Reetu Mukherji, MD, of MedStar Health; and Raji Shameem, MD, of Orlando Health.
Progression during or shortly after immunotherapy generally indicates aggressive biology or preexisting metastatic disease, necessitating consideration of second-line therapy or clinical trials. In these cases, comprehensive biomarker testing, including next-generation sequencing, is critical to guide potential targeted therapy or trial enrollment. Panelists noted parallels with other tumor types, such as bladder and lung cancer, in which progression after immunotherapy similarly informs second-line strategies. The consensus was that although perioperative immunotherapy represents a new standard of care, careful monitoring and timely intervention are essential to optimize outcomes.
Clinical Practice and FDA Approval Implications
The FDA approval of perioperative durvalumab with FLOT for gastric and gastroesophageal junction (GEJ) adenocarcinoma is based on the intent-to-treat population, allowing clinicians to treat all eligible patients regardless of PD-L1 status. Panelists reinforced that the combination therapy does not increase surgical risk, and improvements in event-free survival and pathologic complete response support its use as the new standard. Molecularly, distal esophageal and GEJ tumors are treated similarly, allowing this approach to be extrapolated across these anatomic sites. Patient-centered considerations, including fitness, comorbidities, and treatment tolerance, continue to guide dose adjustments and adjuvant therapy decisions.
Overall, the panel concluded that perioperative durvalumab with FLOT represents a paradigm shift in the management of resectable gastric and GEJ adenocarcinoma. Aggressive monitoring, biomarker-informed therapy, and multidisciplinary collaboration remain essential to optimizing patient outcomes while applying this new standard safely in diverse clinical settings.