Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel for resectable gastric and gastro-oesophageal junction adenocarcinoma (MATTERHORN): final results of overall survival and event-free survival by pathological response in a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial

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• Picked for Radiation Oncology (top studies of the week, 13 September 2026): High-quality evidence in a top journal
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• Picked for Surgical Oncology (top studies of the week, 13 September 2026): Perioperative durvalumab + FLOT for resectable gastric cancer, surgical outcomes
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• Picked for Histology (top studies of the week, 13 September 2026): Durvalumab plus FLOT in gastric cancer trial
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Abstract

BACKGROUND: Durvalumab plus perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) previously improved event-free survival and pathological complete response in resectable gastric and gastro-oesophageal junction adenocarcinoma. We aimed to examine its effect on overall survival. METHODS: MATTERHORN is a global, randomised, double-blind, placebo-controlled, multicentre, phase 3 trial that took place in 147 medical centres in 20 countries (representing Asia, Europe, North America, and South America). Adults with histologically documented resectable gastric or gastro-oesophageal junction adenocarcinoma (eligible for radical surgery; stage II-IVa) not previously treated with anticancer therapy were eligible. Participants were randomly assigned (1:1) to perioperative durvalumab plus FLOT or placebo plus FLOT. Blocked randomisation (unique randomisation number via an interactive response technology system and randomisation and trial supply management system) was stratified by geographical region, clinical lymph node status, and PD-L1 expression. Participants were centrally assigned using the interactive response technology system and randomisation and trial supply management system. Participants received durvalumab 1500 mg or placebo intravenously every 4 weeks on day 1 of each cycle plus FLOT intravenously every 2 weeks on days 1 and 15 of each cycle for four cycles (two neoadjuvant and two adjuvant), followed by durvalumab 1500 mg or placebo intravenously every 4 weeks on day 1 of each cycle for ten additional cycles. Participants, investigators, and those assessing outcomes were masked. The previously reported primary outcome was event-free survival; overall survival in the intention-to-treat population was a key secondary endpoint and is the main endpoint reported here. Safety data were collected throughout treatment and the follow-up period (up to and including 90 days after the last dose of the trial drug) and were analysed in participants who received at least one dose of trial treatment; these data were reported previously and are summarised here. MATTERHORN is closed to recruitment but is ongoing and registered with ClinicalTrials.gov (NCT04592913). FINDINGS: From Nov 17, 2020, to Sept 2, 2022, 1258 participants were enrolled and 948 were randomly assigned; 474 were randomly assigned to durvalumab and 474 to placebo. In a total of 948 participants, the median age was 62 years (IQR 54-68), 682 (72%) were male, and 266 (28%) were female. Overall survival significantly improved in the durvalumab versus placebo group (hazard ratio 0·78, 95% CI 0·63-0·96; p=0·021; significance threshold p<0·0499). Adverse events with the outcome of death possibly related to any trial treatment occurred in 6 (1%) of 475 participants in the durvalumab group and 2 (<1%) of 469 participants in the placebo group. INTERPRETATION: Perioperative durvalumab plus FLOT improved overall survival versus placebo plus FLOT and is a new standard treatment option for patients with resectable gastric or gastro-oesophageal junction adenocarcinoma. FUNDING: AstraZeneca.

Abstract as published, via PubMed.