AstraZeneca’s Imfinzi gains landmark FDA approval for early gastric and gastroesophageal cancers

The FDA recently approved AstraZeneca’s Imfinzi (durvalumab) as the first and only perioperative immunotherapy for patients with resectable, early-stage and locally advanced gastric and gastroesophageal junction (GEJ) cancers. This milestone marks a significant advance in the treatment of a disease where recurrence rates remain high and long-term survival outcomes have historically been poor.

Gastric cancer is the fifth leading cause of cancer death worldwide, with one million new cases diagnosed annually. Until Imfinzi (durvalumab), patients with resectable gastric/GEJ cancers only had chemotherapy (FLOT: fluorouracil, leucovorin, oxaliplatin and docetaxel) as standard of care. Despite surgery and chemo, relapse rates remained high. Until now, no immunotherapy had been approved in the perioperative setting, that is, treatment given both before and after surgery, to improve survival outcomes for these patients.

Other immunotherapies used in gastric cancer include Opdivo (nivolumab), which is approved for advanced or metastatic gastric/GEJ cancers in combination with chemotherapy. Keytruda (pembrolizumab) is approved for advanced gastric/GEJ cancers with PD-L1 expression (CPS ≥1) and for MSI-H/dMMR tumors. Other agents such as Vyloy (trastuzumab, zolbetuximab, etc.) are used in biomarker-driven metastatic settings (HER2-positive, CLDN18.2-positive), but not perioperatively.

The FDA’s decision was based on the priority review of results from the Phase III MATTERHORN trial, which enrolled 948 patients with stage II–IVA resectable gastric and GEJ cancers. The study demonstrated that Imfinzi combined with standard-of-care FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) reduced the risk of disease recurrence, progression, or death by 29% compared to chemotherapy alone. Moreover, the regimen cut the risk of death by 22%, with seven in ten patients alive at three years versus 62% in the chemotherapy-only arm.

Historically, perioperative chemotherapy has been the backbone of treatment for resectable gastric cancer, but outcomes remained suboptimal. The MATTERHORN trial is the first Phase III study to show statistically significant event-free survival improvement with immunotherapy in this setting, establishing a new standard of care. Imfinzi can now be used with chemotherapy before surgery, then after surgery with chemotherapy and on its own as a monotherapy.

Yelena Y. Janjigian, M.D., from Memorial Sloan Kettering Cancer Center and principal investigator in the trial, emphasized, “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.”

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Hematology Business Unit, highlighted the broader implications: “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.”

Imfinzi’s approval represents a transformative step in gastric cancer care, offering patients a chance at longer survival and reduced recurrence risk. By bridging the gap between surgery and systemic therapy with immunotherapy, this regimen redefines curative-intent treatment and provides hope in a disease long marked by poor outcomes.