Adding immunotherapy to standard treatment both before and after surgery significantly improved outcomes for people with gastric and gastroesophageal adenocarcinoma (G/GEA), according to experts from Memorial Sloan Kettering Cancer Center (MSK). Results from the MATTERHORN trial, a global phase three study, were presented today at the annual American Society of Clinical Oncology meeting and simultaneously published in the New England Journal of Medicine (NEJM).
The trial met its primary endpoint, showing a significant improvement in event-free survival – the amount of time that someone lives post-treatment without any sign of recurrence. After two years, 67.4% of patients who received immunotherapy in addition to the standard treatment were alive without any indication of cancer progression compared to 58.5% in the placebo group.
Surgery and the chemotherapy regimen of FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) are the current standard of care, but these cancers are some of the deadliest worldwide. Cure rates remain low at approximately 40%, with most patients who relapse doing so within three years of surgery. The five-year survival is also poor, with less than half of the patients alive at five years. The challenge, according to experts, has been exploring new and novel treatments that would give people a better chance at long-term survival.
“This is a major step forward for patients facing this difficult diagnosis,” said Yelena Y. Janjigian, MD, Chief of the Gastrointestinal Oncology Service at MSK, global principal investigator of the trial, and first author of the NEJM submission. “To be able to tell a patient that their cancer has completely responded to treatment—and that they are cured—is one of the most rewarding moments in oncology. These results bring us closer to making that outcome a reality for many more patients worldwide.”
The large, double-blind, randomized study (NCT04592913) included durvalumab from AstraZeneca, an immune checkpoint inhibitor that works by helping the immune system recognize and attack cancer cells. Immunotherapy has shown promise in treating various cancers, including some resistant to other treatments. In this trial, half the patients received durvalumab every four weeks alongside standard chemotherapy and then continued durvalumab alone after surgery; the trial’s other arm received a placebo on the same schedule.
Additionally, overall survival (OS) - a key secondary endpoint - was improved in the durvalumab arm, and the pathological complete response rate, indicating no remaining cancer detected at surgery, was significantly higher with durvalumab than placebo, 19.2% versus 7.2%, respectively. Adding durvalumab didn’t delay surgery or recovery, and the rate of serious side effects was similar between the groups.
When Will Murray was diagnosed with esophageal cancer in 2022, he joined the clinical trial. “Everything I read and heard about the type of cancer I had was grim,” he said. “Then I met the MSK team and discussed the trial with Dr. Janjigian, and I felt optimistic. Her approach was different. I truly believe this trial saved my life.”
Final OS data will be reported in 2026 after sufficient time has passed to give an accurate assessment.
The Phase three study was sponsored by AstraZeneca. See here for ASCO 2025 LBA5. Access disclosures for Dr. Janjigian here.
Contact
Andrea Fassacesia
fassaca1@mskcc.org