Durvalumab Plus FLOT Boosts Survival in Resectable Gastric and GEJ Cancer, MATTERHORN Shows

Final results from the phase 3 MATTERHORN trial, published in The Lancet, show that adding AstraZeneca’s durvalumab to perioperative FLOT chemotherapy improved both overall survival and event-free survival for patients with resectable gastric or gastro-oesophageal junction adenocarcinoma, a major result in curative-intent treatment for these cancers.

The global, randomized, double-blind, placebo-controlled study enrolled 948 patients with resectable disease and assigned them evenly to durvalumab plus FLOT or placebo plus FLOT. FLOT is a four-drug chemotherapy regimen of fluorouracil, leucovorin, oxaliplatin and docetaxel. Perioperative treatment means therapy given before and after surgery; in MATTERHORN, patients also continued durvalumab or placebo after surgery as monotherapy for up to about a year. The trial is registered as NCT04592913.

MATTERHORN had already met its primary endpoint of event-free survival, which measures outcomes such as disease progression, recurrence or death. At the interim analysis, the durvalumab regimen cut the risk of one of those events by 29% versus FLOT alone, with a hazard ratio of 0.71 and a statistically significant P value below .001. Two-year event-free survival was 67.4% in the durvalumab group, compared with 58.5% in the placebo group. Median event-free survival was not reached with durvalumab and was 32.8 months in the control arm.

The final overall survival analysis also showed a statistically significant benefit. The hazard ratio for death was 0.78, indicating a 22% reduction in the risk of death versus placebo plus FLOT, with a P value of .021. Median overall survival was not reached in either group, but reports tied to the final analysis put 36-month overall survival at about 68.6% with durvalumab and 61.9% with placebo.

Other findings also favored the immunotherapy combination. Pathological complete response — meaning no residual viable tumor seen in the resected specimen after preoperative treatment — was 19.2% with durvalumab versus 7.2% with placebo by central review. Safety was broadly similar between the groups for severe side effects: grade 3 or 4 adverse events occurred in about 71.6% of patients given durvalumab and 71.2% of those given placebo. Immune-mediated side effects were more common with durvalumab, as expected for a PD-L1 inhibitor, but investigators reported no new safety signals and no meaningful delay to surgery or postoperative treatment.

The results matter because recurrence has remained a major problem for patients treated with surgery and perioperative chemotherapy alone. Before MATTERHORN, perioperative FLOT was already a standard option for many patients with resectable gastric and gastro-oesophageal junction adenocarcinoma. What set MATTERHORN apart is that earlier perioperative immunotherapy studies in this setting had improved pathological response without clearly delivering the same phase 3 survival outcome. MATTERHORN is the key trial to show that adding a PD-L1 drug to FLOT in a broad, all-comer population can improve both event-free survival and overall survival.

The data had already reshaped regulation before publication of the final report. The U.S. Food and Drug Administration approved durvalumab with perioperative FLOT for adults with resectable gastric or gastro-oesophageal junction adenocarcinoma on Nov. 25, 2025. The European Union followed with approval in 2026 after a positive opinion from the Committee for Medicinal Products for Human Use, the European Medicines Agency panel that reviews medicines for the bloc.

AstraZeneca, which markets durvalumab as Imfinzi, sponsored and funded the trial. Investigators reported industry relationships in the study disclosures.