Ep. 1: Clinical Insights on Perioperative Durvalumab in Gastric and GEJ Cancer
Key Points
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Perioperative durvalumab with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy improves event-free survival (EFS) in gastric and gastroesophageal junction (GEJ) adenocarcinoma.
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Immunotherapy does not compromise surgical outcomes, and most patients tolerate therapy with manageable toxicity.
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Certain patients with active autoimmune disease remain ineligible, highlighting the importance of individualized treatment decisions.
MATTERHORN Study Design and Efficacy
In 2025, multiple drug approvals reshaped oncology care, with perioperative durvalumab standing out based on the MATTERHORN study. Oncology Brothers cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, discussed this therapy with a panel consisting of 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.
Dr. Maron opened the discussion by describing the trial design: Patients received 4 cycles of FLOT chemotherapy, followed by surgery and then 4 cycles of FLOT combined with either durvalumab or placebo. “Patients also received an additional 10 months of adjuvant durvalumab alone every 4 weeks,” he said.
Initial data showed a significant increase in pathologic complete response, from 7% to 19%, with the addition of durvalumab. Updated EFS at 2 years was 67% versus 59% for FLOT alone, confirming the regimen’s superiority.
Safety, Surgical Outcomes, and Patient Selection
The panelists stressed that adding durvalumab to FLOT does not compromise surgery. Dr. Alistar explained that toxicity is largely driven by chemotherapy rather than immunotherapy, and autoimmune reactions were rare. Surgical completion rates were similar between arms, with 10% to 15% of patients in each arm not reaching surgery, indicating that perioperative durvalumab can be safely incorporated into standard practice.
Patient selection remains essential, as active autoimmune diseases such as Crohn disease or ulcerative colitis may preclude immunotherapy. “There are certain patients who are not candidates who would not be able to receive any immunotherapy agent,” Dr. Shameem noted, emphasizing the need for careful evaluation. Dose modifications of FLOT are feasible, and ongoing communication with patients allows for safe delivery of therapy, even for those needing adjustments.