The European Commission has approved Imfinzi (durvalumab) in combination with FLOT chemotherapy as the first perioperative immunotherapy for adults with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers. The Imfinzi EU approval, announced by AstraZeneca on 16 March 2026, represents the third perioperative indication for an Imfinzi-based regimen in Europe, following earlier approvals in resectable non-small cell lung cancer and muscle-invasive bladder cancer. Durvalumab is a human monoclonal antibody that blocks PD-L1, releasing immune inhibition against tumour cells. Gastric cancer is the fifth leading cause of cancer death globally, with nearly one million diagnoses annually; in 2024, roughly 15,500 drug-treated patients in the EU had early-stage or locally advanced gastric or GEJ cancer, the company said.
The approval covers a perioperative regimen consisting of two cycles of Imfinzi plus FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) before surgery, followed by two cycles of Imfinzi plus FLOT after surgery, and then Imfinzi monotherapy for up to ten additional cycles. The European Commission decision followed a positive opinion from the Committee for Medicinal Products for Human Use. Imfinzi and FLOT chemotherapy is already approved in the US and other countries for this indication, and regulatory applications are under review in Japan and several additional markets.
The approval was based on the MATTERHORN Phase III trial, a randomised, double-blind, placebo-controlled study that enrolled 948 patients across 176 centres in 20 countries. In a planned interim analysis of the primary endpoint, event-free survival, patients treated with the durvalumab-based regimen showed a 29% reduction in the risk of disease progression, recurrence, or death compared to chemotherapy alone (hazard ratio 0.71; 95% CI 0.58–0.86; p<0.001). Median EFS was not reached in the Imfinzi arm versus 32.8 months in the comparator arm. At 24 months, 67.4% of patients in the Imfinzi arm were event-free compared to 58.5% with chemotherapy alone. The final overall survival analysis showed a 22% reduction in the risk of death (HR 0.78; 95% CI 0.63–0.96; p=0.021), with an estimated 69% of patients in the Imfinzi arm alive at three years versus 62% in the comparator arm. The overall survival benefit was observed regardless of tumour PD-L1 status. Grade 3 or higher adverse events were similar between arms (71.6% versus 71.2%), and surgery completion rates were comparable, indicating that the addition of durvalumab did not compromise surgical feasibility. Results were published in The New England Journal of Medicine and presented at the European Society for Medical Oncology Congress 2025.
This approval addresses a setting where recurrence remains common despite curative-intent surgery and chemotherapy; approximately one in four patients develop recurrent disease within one year, and fewer than half survive to five years. No other immunotherapy has secured a perioperative approval for gastric cancer. Competing PD-1 inhibitors have been tested in this space but have not achieved comparable regulatory milestones: Merck's pembrolizumab, evaluated in the KEYNOTE-585 trial, improved pathological complete response rates but did not meet its primary EFS endpoint, while Bristol-Myers Squibb's nivolumab, tested in ATTRACTION-05, did not demonstrate a statistically significant relapse-free survival benefit in the adjuvant-only setting. The perioperative gastric cancer pipeline includes several agents in Phase II/III development, among them BeiGene's tislelizumab, Akeso's cadonilimab (a PD-1/CTLA-4 bispecific), and AstraZeneca's own rilvegostomig (a PD-1/TIGIT bispecific). Claudin 18.2-directed therapies, including Astellas' zolbetuximab and AstraZeneca's sonesitatug vedotin, are also under investigation but remain approved only for advanced disease. The durvalumab gastric cancer data from MATTERHORN now establish the benchmark against which these perioperative programmes will be measured.
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