MATTERHORN: Durvalumab + FLOT Delivers an Overall Survival Benefit: The Lancet | September 2026

What Did the Study Find?

MATTERHORN randomized 948 patients with resectable gastric or gastro-oesophageal junction adenocarcinoma to perioperative durvalumab + FLOT or placebo + FLOT.

Durvalumab significantly improved overall survival, reducing the risk of death by 22% (HR 0.78).

This confirms the previously demonstrated event-free survival benefit (HR 0.71).

Pathological complete response was also substantially higher with durvalumab: 19% vs 7%.

Benefit therefore extends across pCR, EFS and now OS—three complementary efficacy endpoints.

Adding durvalumab did not compromise surgical feasibility or introduce unexpected safety concerns.

Treatment-related deaths were uncommon but numerically higher with durvalumab (1% vs <1%).

Why Does It Matter?

Previous perioperative immunotherapy trials produced mixed results. MATTERHORN is the first phase III trial to demonstrate a definitive survival benefit from adding immunotherapy to modern perioperative FLOT.

GastroAGI Takeaway

This is practice-changing. Perioperative durvalumab + FLOT establishes a new standard treatment option for eligible patients with resectable gastric/GEJ adenocarcinoma, moving immunotherapy firmly into the curative-intent setting.