- Results from the MATTERHORN phase 3 study demonstrate that immunotherapy in combination with standard chemotherapy before and after surgery significantly improves event-free survival in patients with operable and localized gastric and gastroesophaegeal junction cancers.
- In patients assigned to the investigational combination of the monoclonal antibody durvalumab plus FLOT chemotherapy, the median event-free survival and median overall survival were not reached, meaning that at the time of analysis 50% of patients enrolled in this study were still alive and had not experienced recurrence or progression of disease, or other adverse events.
- MATTERHORN is the first global, randomized phase 3 study to show superior event-free survival with an immunotherapy combination versus standard-of-care in this setting.
- Second interim analysis of efficacy and safety from this multi-center study, co-led by Josep Tabernero, Head of the Medical Oncology Department at the Vall d’Hebron University Hospital and VHIO’s Director, were presented today at the Plenary Session of the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. These data published simultaneously in The New England Journal of Medicine.
Results from the MATTERHORN global, randomized phase 3 trial—co-led by Josep Tabernero Head of the Medical Oncology Department at the Vall d’Hebron University Hospital and VHIO’s Director—show that perioperative treatment with the monoclonal antibody and immune checkpoint inhibitor durvalumab in combination with standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy significantly improves event-free survival in resectable, localized gastric and gastroesophageal junction cancers.
The findings, presented today at the Plenary Session of the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting1 by first author Yelena Y. Janjigian, Chief Attending Physician of the Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, published simultaneously in The New England Journal of Medicine2.
There were over 968,000 new cases of gastric (stomach) cancer in 2022 and almost 660,000 deaths, ranking the disease as fifth in terms of both incidence and mortality worldwide3. Gastroesophageal junction (GEJ) adenocarcinoma is a type of gastric cancer that develops where the oesophagus connects to the stomach.
“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 Investigator of the MATTERHORN 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 FLOT versus placebo plus FLOT in patients with resectable, localized gastric and gastroesophageal junction cancers. 948 patients were randomized (1:1) to receive treatment with durvalumab in combination with FLOT chemotherapy or placebo plus chemotherapy prior to surgery. This was followed by adjuvant durvalumab plus chemotherapy, then durvalumab monotherapy, or placebo plus chemotherapy and placebo monotherapy after surgery.
At a median follow-up of 31.5 months, median event-free survival and median overall survival were not reached in patients assigned to durvalumab plus chemotherapy, meaning that at the time of analysis 50% of patients enrolled in this study were still alive and had not experienced recurrence or progression of disease, or other adverse events, compared to a median event-free survival of 32.8 months and median overall survival of 47.2 months in patients who received placebo plus FLOT chemotherapy.
“The addition of perioperative immunotherapy to standard treatment with chemotherapy showed a clinically meaningful improvement in patient outcomes, including disease control and an encouraging trend in overall survival. Results from this study support this therapeutic strategy as a potential new standard-of-care for patients with resectable, localized gastric and gastroesophageal junction cancers,” concluded Josep Tabernero.
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References
- 2025 ASCO Annual Meeting, May 30 – June 3, Chicago, IL
Corresponding session details:
Plenary Session
Date: June 1, 2025
Time: 13:00h CT, 20:00h CEST
Room: Hall B1
LAB 5. Event-free survival (EFS) in MATTERHORN: A randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC). 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 H. Moehler, Marcelo Garrido, Sulene S. Oliveira, Moishe Liberman, Victor Castro Oliden, Elizabeth C. Smyth, Olivier Serrano, Eric Heilbron, Alejandra Negro, Josep Tabernero.
- Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263.
- 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 H. Moehler, Marcelo Garrido, Sulene S. Oliveira, Moishe Liberman, Victor Castro Oliden, Elizabeth C. Smyth, Olivier Serrano, Eric Heilbron, Alejandra Negro, Josep Tabernero. N Engl J Med. 2025 Jun 1. doi: 10.1056/NEJMoa2503701. Epub ahead of print. https://www.nejm.org/doi/full/10.1056/NEJMoa2503701
