EU approves AstraZeneca’s Imfinzi with FLOT chemotherapy for resectable gastric and GEJ cancers after MATTERHORN Phase III trial showed significant survival benefit
Written By: Marka Sheshi, PharmD
Reviewed By: Pharmacally Editorial Team
The European Commission has approved Imfinzi (durvalumab) in combination with FLOT chemotherapy for the treatment of adults with resectable early-stage and locally advanced gastric and gastroesophageal junction (GEJ) cancers (Stages II–IVA).
The perioperative regimen includes two cycles of Imfinzi with chemotherapy before surgery and two cycles after surgery, followed by Imfinzi monotherapy.
The approval follows a positive opinion from the European Medicines Agency Committee for Medicinal Products for Human Use and is based on results from the Phase III MATTERHORN Phase III trial (NCT04592913), published in the New England Journal of Medicine.
In the randomized, double-blind study involving 948 patients with resectable Stage II–IVA gastric or GEJ cancers, the Imfinzi-based perioperative regimen reduced the risk of disease progression, recurrence or death by 29% compared with chemotherapy alone (event-free survival HR 0.71; 95% CI 0.58–0.86; p<0.001). Median event-free survival was not reached in the Imfinzi arm versus 32.8 months in the control group. At 24 months, 67.4% of patients receiving Imfinzi remained event-free compared with 58.5% with chemotherapy alone.
Final overall survival results showed the regimen reduced the risk of death by 22% compared with chemotherapy alone (HR 0.78; 95% CI 0.63–0.96; p=0.021). At three years, 69% of patients treated with the Imfinzi-based regimen were alive versus 62% in the comparator arm, with survival curves continuing to separate over time. The survival benefit was observed regardless of tumor PD-L1 expression.
The safety profile of the combination was consistent with known profiles of each therapy. Grade 3 or higher adverse events occurred in 71.6% of patients receiving Imfinzi plus FLOT and 71.2% with chemotherapy alone, and the proportion of patients completing surgery was similar between groups.
According to Josep Tabernero, MD, PhD, principal investigator of the MATTERHORN trial, recurrence remains common in resectable gastric and GEJ cancers despite curative surgery and chemotherapy, and the durvalumab-based perioperative regimen offers an opportunity to improve long-term survival.
Gastric cancer is the fifth leading cause of cancer death globally, with nearly one million new cases diagnosed each year. In 2024, an estimated 15,500 patients in the EU received drug treatment for early-stage or locally advanced gastric and GEJ cancers.
The Imfinzi and FLOT perioperative regimen is already approved in the United States and several other countries, with regulatory submissions under review in Japan and additional regions.
References
Imfinzi approved in the EU as first and only perioperative immunotherapy for patients with early gastric and gastroesophageal cancers, 16 March 2026, https://chatgpt.com/c/69b83b39-9830-8320-9ba8-3f72ef76f8d6
Yelena Y. Janjigian et al, Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer, N Engl J Med 2025;393:217-230, https://www.nejm.org/doi/abs/10.1056/NEJMoa2503701
Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer, ClinicalTrials.gov ID NCT04592913, https://clinicaltrials.gov/study/NCT04592913
About the Writer
Marka Sheshi | Doctor of Pharmacy
Driven by a deep commitment to clinical excellence, research integrity, and impactful medical writing. With a strong foundation in pharmacotherapy and patient safety, specializes in transforming complex scientific evidence into authoritative, publication-ready content. Passionate about advancing healthcare through precise, evidence-based communication that informs practice, strengthens research visibility, and improves patient outcomes.