- Results of final overall survival analysis from the global, randomized phase 3 MATTERHORN clinical trial show that adding perioperative durvalumab to standard chemotherapy reduced the risk of death by 22% compared with placebo plus chemotherapy in patients with localized, resectable gastric or gastroesophageal junction cancer.
- Reported in The Lancet, final overall survival analysis supports this new perioperative combination as a new standard treatment option for this patient population.
- Co-directed by Josep Tabernero, the MATTERHORN study enrolled participants at 147 medical centers in 20 countries across Europe, Asia, North America, and South America.
Published in The Lancet*, final results of overall survival from the phase 3 MATTERHORN clinical trial show that adding the antibody durvalumab, an immune checkpoint inhibitor, to the standard pre- and postoperative chemotherapy regimen improves survival in patients with operable, localized gastric or gastroesophageal junction cancer.
Co-directed by Josep Tabernero, Head of the Medical Oncology Department at Vall d’Hebron University Hospital and Director of the Vall d’Hebron Institute of Oncology, this international study included 948 patients from 147 medical centers across 20 countries in Europe, Asia, North America, and South America, who were randomized (1:1) to receive treatment with durvalumab in combination with standard FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy, or placebo plus FLOT before and after surgery.
A global health challenge
Gastric cancer is the fifth most common cancer worldwide and accounts for nearly 5% of all new cancer diagnoses, with almost one million new cases annually across the globe. It has a particularly high incidence in people over the age of 65 and is approximately twice as common in men as in women. Gastric and gastroesophageal junction cancer represent a global health challenge.
“Complete surgical resection is the cornerstone of treatment for localized gastric or gastroesophageal junction cancer. In most Western countries, the FLOT three-drug chemotherapy regimen is the standard-of-care for this patient population, given before and after surgery,” said Josep Tabernero, senior author of the study.
“While advances in treatment have improved survival, the prognosis of patients with gastric cancer is often poor. Due to late-stage diagnosis and the aggressive nature of the disease, the overall five-year survival rate is 33% in the U.S. and 25% globally, representing an unmet clinical challenge,” added Tabernero.
The phase 3 MATTERHORN clinical trial assessed the efficacy of the combination of perioperative durvalumab and standard FLOT chemotherapy versus placebo plus FLOT in patients with resectable, localized gastric or gastroesophageal junction cancers. This study had previously met its primary endpoint by demonstrating a statistically significant improvement in event-free survival with durvalumab plus FLOT versus placebo plus FLOT.
Results of final overall survival analysis further confirm this benefit: durvalumab plus FLOT demonstrated a statistically significant and clinically relevant improvement in overall survival compared with placebo plus FLOT.
After a median follow-up of 43 months, patients who received immunotherapy plus FLOT showed a statistically and clinically significant improvement in overall survival compared with those who received placebo plus FLOT, with a 22% reduction in the risk of death. Although the medians were not reached in either arm, after three years of follow-up, 69% of patients treated with durvalumab were still alive, compared with 62% in the control group.
Overall survival improved across all patient subgroups, regardless of their PD-L1 expression levels or pathological nodal status.
“These results position this perioperative regimen as the first immunotherapy strategy to demonstrate prolonged survival in patients with early-stage gastric or gastroesophageal junction cancer, and point to a new standard of care,” he concluded.
Based on results from the MATTEHORN trial, the European Medicines Agency (EMA) approved the use of durvalumab in combination with chemotherapy last March as the first and only perioperative immunotherapy for patients with early-stage gastric or gastroesophageal junction cancer.
The indication is already approved in the United States and other countries as well, while regulatory applications remain under review in Japan and other markets.
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Reference
*Yelena Y Janjigian, Salah-Eddin Al-Batran, Zev A Wainberg, Kei Muro, Daniela Molena, Eric Van Cutsem, Woo Jin Hyung, Lucjan Wyrwicz, Do-Youn Oh, Takeshi Omori, Markus Moehler, Arinilda C Bragagnoli, Gabriel Garbaos, Moishe Liberman, María Luisa Limón Mirón, Elizabeth C Smyth, Lin-Yang Cheng, Scott H Robbins, Nicola Valeri, Ioannis Xynos, Josep Tabernero, on behalf of the MATTERHORN investigators. 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. The Lancet 2026; 0 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01254-7/fulltext
