AstraZeneca’s Imfinzi Regimen Shows Strong EFS And OS Benefits In FDA-Backed MATTERHORN Trial

AstraZeneca has received US FDA approval for Imfinzi (durvalumab) combined with standard FLOT chemotherapy as a perioperative treatment for adults with resectable, early-stage, and locally advanced gastric or gastroesophageal junction cancers. The regimen includes neoadjuvant Imfinzi plus chemotherapy before surgery, followed by adjuvant therapy and Imfinzi monotherapy. The decision follows a Priority Review based on strong outcomes in the Phase III MATTERHORN trial.

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.”

Data from MATTERHORN showed significant improvements in both event-free survival (EFS) and overall survival (OS). Patients receiving the Imfinzi-based regimen demonstrated a 29% reduction in the risk of disease progression, recurrence, or death compared with chemotherapy alone. Early results showed higher one-year and two-year EFS rates in the Imfinzi arm, with median EFS not yet reached. Final OS analysis revealed a 22% reduction in the risk of death, with long-term survival curves showing increasing benefit over time across all PD-L1 subgroups.

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: “Today’s 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.”

Safety findings were consistent with known profiles of Imfinzi and FLOT, with no new concerns and similar surgery completion and adverse event rates across treatment arms. The FDA submission was reviewed under Project Orbis, enabling parallel regulatory reviews in other countries including Australia, Canada, and Switzerland. Additional applications remain under assessment in the EU, Japan, and several global markets.

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. Today’s approval represents a major step forward in improving outcomes and offering renewed hope to those affected by this devastating disease.”