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FDA approves durvalumab in combination with standard-of-care FLOT chemotherapy in patients with gastric and gastroesophageal junction cancers

On November 25, 2025, the U.S. Food and Drug Administration (FDA) approved durvalumab, an anti-programmed death ligand 1 (PD-L1) antibody, with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy as neoadjuvant and adjuvant treatment, followed by single agent durvalumab, for adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).1

Despite curative-intent surgery and perioperative chemotherapy, recurrence rates in this population remain high, with fewer than half of patients surviving beyond five years.2 This approval represents the first immunotherapy to demonstrate improved event-free survival in resectable GC/GEJC, addressing a critical unmet need in this patient population.

The approval is based on efficacy data from MATTERHORN (NCT04592913), a randomized, double-blind, placebo-controlled, multicenter Phase III trial conducted in 948 patients with previously untreated, resectable Stage II to Stage IVa GC/GEJC. Patients were randomized 1:1 to receive either durvalumab plus FLOT or placebo plus FLOT. The major efficacy outcome measure was event-free survival (EFS), with additional endpoints including overall survival (OS) and pathological complete response (pCR) rate.1

Median EFS was not reached (95% CI: 40.7, not estimable) in the durvalumab plus FLOT arm and was 32.8 months (95% CI: 27.9, not estimable) in the placebo plus FLOT arm (hazard ratio 0.71; 95% CI: 0.58, 0.86; p<0.001).1 Two-year EFS was 67.4% in the durvalumab group compared to 58.5% in the placebo group.3 Median OS was not reached in both arms (HR 0.78; 95% CI: 0.63, 0.96; p=0.021). The pCR rate was 19.2% (95% CI: 15.7, 23.0) in the durvalumab arm and 7.2% (95% CI: 5.0, 9.9) in the placebo arm (p<0.001).1

Yelena Janjigian, MD, Memorial Sloan Kettering Cancer Center, New York, NY, and principal investigator of the trial, commented on recent patient-reported outcome (PRO) from the study:

“In MATTERHORN, patient-reported outcomes and the quality of life measures are equivalent in both arms. Durvalumab does not negatively impact outcomes and how patients tolerate this regimen, which is, of course, very reassuring to see because it’s a practice-changing, global new standard.”

This approval marks a significant advance in the perioperative treatment of resectable GC/GEJC, establishing durvalumab plus FLOT as a new treatment option that addresses the high recurrence rates seen with chemotherapy alone.

References:

  1. Center for Drug Evaluation and Research. FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma [Internet]. U.S. Food and Drug Administration. 2025 [cited 2025 Nov 26]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-resectable-gastric-or-gastroesophageal-junction-adenocarcinoma
  2. Perioperative treatment with durvalumab and FLOT chemotherapy can reduce risk of recurrence for some patients with gastric cancers [Internet]. American Society of Clinical Oncology. 2025 [cited 2025 Nov 26]. Available from: https://www.asco.org/about-asco/press-center/news-releases/perioperative-treatment-with-durvalumab-FLOT-chemotherapy
  3. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. N Engl J Med. 2025;393(3):217-230. doi:10.1056/NEJMoa2503701

Written by Stephanie Coombe-Whitlock