AstraZeneca Imfinzi gets USFDA okay for early gastric and gastroesophageal cancers

The approval follows Priority Review by the Food and Drug Administration (FDA) and is based on event-free survival (EFS) and overall survival (OS) data from the MATTERHORN Phase III trial. The EFS results were presented during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine. OS results from MATTERHORN were presented in a Proffered Paper session at the European Society for Medical Oncology (ESMO) Congress 2025.

Gastric cancer is the fifth leading cause of cancer death globally, with nearly one million people diagnosed each year. In 2024, there were roughly 6,500 drug-treated patients in the US in early-stage and locally advanced gastric or GEJ cancer.

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said, “This approval ushers in a new clinical paradigm for patients with early gastric and gastroesophageal junction cancers, with Imfinzi plus FLOT delivering a durable survival benefit that increases over time. As the third US approval for a perioperative Imfinzi-based regimen, this milestone further validates the perioperative approach and underscores our focus on bringing novel treatments to early-stage cancers where cure is the goal.”

Yelena Y. Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center (MSK), New York and principal investigator in the MATTERHORN trial, said, “The approval marks the first immunotherapy regimen approved in the neoadjuvant setting for gastric and gastroesophageal junction cancers—with durvalumab demonstrating a clear overall survival benefit and opening an entirely new chapter in the treatment of early-stage disease. Nearly seven in 10 patients were alive at three years following treatment with the durvalumab-based perioperative regimen. This survival benefit, observed regardless of PD-L1 status, establishes a new standard of care in this curative-intent setting.”

Aki Smith, Founder and Executive Director, Hope for Stomach Cancer, said, “From personal experience as a caregiver to my father, I know that for too long patients diagnosed with early gastric or gastroesophageal junction cancer have faced a high risk of their cancer returning, even after undergoing surgery and therapy intended to cure it. The approval represents a major step forward in improving outcomes and offering renewed hope to those affected by this devastating disease.”

In a planned interim analysis, patients treated with the Imfinzi-based perioperative regimen showed a 29% reduction in the risk of disease progression, recurrence or death versus chemotherapy alone (based on an EFS hazard ratio [HR] of 0.71; 95% confidence interval [CI] 0.58-0.86; p<0.001). Estimated median EFS was not yet reached for the Imfinzi arm versus 32.8 months for the comparator arm. An estimated 78.2% of patients treated with the Imfinzi-based perioperative regimen were event-free at one year, compared to 74.0% in the comparator arm; the estimated 24-month EFS rate was 67.4% versus 58.5%, respectively.

In the final OS analysis, results showed the Imfinzi and FLOT perioperative regimen reduced the risk of death by 22% compared with chemotherapy alone (based on a HR of 0.78; 95% CI 0.63-0.96; p=0.021). An estimated 69% of patients treated with the Imfinzi-based regimen were alive at three years compared with 62% in the FLOT-only arm. With longer follow-up, the OS curves showed continued separation, signaling a greater magnitude of benefit over time for the Imfinzi-based regimen. An OS benefit was observed regardless of PD-L1 status.

The safety profile for Imfinzi and FLOT chemotherapy was consistent with the known profiles of each medicine, and the percentage of patients that completed surgery was similar compared to chemotherapy alone. Grade 3 or higher adverse events due to any cause were similar between the two arms (71.6% for Imfinzi and FLOT arm; 71.2% for FLOT-only arm).

The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, the Imfinzi and FLOT perioperative regimen is also under review by regulatory authorities in Australia, Canada, and Switzerland for the same indication. Regulatory applications are also under review in the European Union (EU), Japan and several other countries.

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