By Marcus A. Banks

Adding the immunotherapy durvalumab (Imfinzi, AstraZeneca) to a standard chemotherapy regimen improves outcomes for people with resectable gastric or gastroesophageal junction cancer, per results of the phase 3 MATTERHORN trial presented at the 2025 ASCO Annual Meeting, in Chicago.

“I’m pleased to report that MATTERHORN met its primary end point of event-free survival [EFS],” said principal investigator Yelena Janjigian, MD, the chief of gastrointestinal medical oncology at Memorial Sloan Kettering Cancer Center, in New York City. Study results were simultaneously published in The New England Journal of Medicine (2025 Jun 1. doi:10.1056/NEJMoa2503701).

More than 1.2 million people worldwide will die of gastric or esophageal cancer in 2025, Dr. Janjigian noted, citing the International Agency for Research on Cancer.

“We need to do better,” she said.

The current standard of care for these cancers is a chemotherapy regimen known as FLOT (5-fluorouracil, leucovorin, oxaliplatin and docetaxel). In the investigational arm of the trial (n=474 adults), adding durvalumab to FLOT led to a median EFS of 40.7 months; the EFS for FLOT plus placebo (n=474 adults) was 32.8 months (hazard ratio, 0.71; 95% CI, 0.58-0.86, P<0.001).

“This translates to a 29% relative risk reduction in disease recurrence, progression or death,” Dr. Janjigian said. “There was an early and sustained separation in the event-free survival curves.” For example, at 24 months 67% of people in the durvalumab arm had not experienced any new cancerous events, compared with 59% in the FLOT plus placebo arm.

Overall survival (OS) curves begin to separate at 12 months, although Dr. Janjigian noted that the OS difference to date does not meet prespecified criteria for statistical significance. The final OS analysis is pending, she added.

MATTERHORN included participants in Asia, Europe, and North and South America, all of whom had resectable stage II to IVa gastric or gastric esophageal junction cancer, with no metastases or prior therapy. “This is one of the most globally representative trials in gastric and esophageal cancer,” Dr. Janjigian said. 

Patients in the durvalumab arm received two cycles of neoadjuvant durvalumab plus FLOT before surgery to resect cancerous tissue, and up to 12 more cycles of durvalumab after surgery during the following year’s adjuvant phase. Tumors were completely removed in 92% of patients in both arms, and adverse events were balanced between arms. This included the most serious adverse event, neutropenia.

“The addition of durvalumab did not negatively impact FLOT delivery or completion of surgery,” Dr. Janjigian said. “MATTERHORN supports global adoption of perioperative durvalumab plus FLOT as a new standard for patients with localized gastric and gastroesophageal adenocarcinoma.”

Dr. Janjigian reported research funding from AstraZeneca.