Written By: Pharmacally Medical News Desk
The FDA has approved Imfinzi (durvalumab) combined with standard chemotherapy (FLOT regimen) as the first and only perioperative immunotherapy for adults with resectable early-stage and locally advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. This landmark approval marks a new clinical paradigm, offering patients a treatment that includes neoadjuvant and adjuvant immunotherapy alongside chemotherapy, significantly improving survival outcomes.
Imfinzi (durvalumab) is a fully human monoclonal antibody that targets PD-L1, a protein on cancer cells that suppresses immune responses, enabling the immune system to attack tumors more effectively as a checkpoint inhibitor. Developed by AstraZeneca, it is administered intravenously and has received multiple FDA approvals for various cancers.
Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, and AstraZeneca said “This approval ushers in a new clinical paradigm for early gastric and gastroesophageal cancers, with Imfinzi plus FLOT delivering a durable and increasing survival benefit. It validates the perioperative approach and reflects our focus on novel treatments aimed at curing early-stage cancers.”
Imfinzi’s approval was based on results from the Phase III MATTERHORN clinical trial (NCT04592913) enrolling 948 patients with resectable stages II to IVA gastric or GEJ cancer. The trial demonstrated that Imfinzi plus FLOT chemotherapy reduced the risk of death by 22% compared to chemotherapy alone, with a hazard ratio (HR) of 0.78 and a statistically significant p-value of 0.021. Three-year overall survival was 69% in the Imfinzi group versus 62% in the chemotherapy-only group. The regimen also showed a 29% reduction in disease progression, recurrence, or death risk (event-free survival, EFS) compared to chemotherapy alone, regardless of PD-L1 status or lymph node involvement. Importantly, the survival benefit increased over time, signaling durable efficacy of the immunotherapy combination.
The treatment protocol involves Imfinzi being administered alongside fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy as neoadjuvant (before surgery) and adjuvant (after surgery) therapy, followed by single-agent Imfinzi maintenance therapy. The safety profile was consistent with prior studies, with no new safety signals, and similar surgical completion rates compared to chemotherapy alone. Grade 3 or higher adverse events were comparable between the treatment arms.
This approval is significant as it establishes Imfinzi as the first immunotherapy regimen approved for perioperative use in early gastric and gastroesophageal cancers, offering a new standard of care aimed at reducing cancer recurrence after surgery. The approval reflects a transformative step in managing these cancers, focusing on improving long-term survival outcomes for patients with resectable disease.
Gastric cancer originates in the stomach lining, while gastroesophageal junction (GEJ) cancer forms at the junction between the esophagus and stomach, often classified together due to similar aggressive behaviors and risk factors like Helicobacter pylori infection, smoking, and diet. These adenocarcinoma types are challenging in early stages, with high recurrence rates post-surgery despite chemotherapy, affecting over 26,000 new U.S. cases annually and carrying poor prognosis if advanced.
Yelena Y. Janjigian, MD, Chief Attending Physician, Memorial Sloan Kettering Cancer Center and MATTERHORN trial investigator said “This is the first immunotherapy regimen approved in the neoadjuvant setting for gastric and gastroesophageal cancers, showing a clear overall survival benefit and setting a new standard of care. Nearly 70% of patients were alive at three years regardless of PD-L1 status.”
Aki Smith, Founder and Executive Director, Hope for Stomach Cancer stated “As a caregiver, I know patients have faced high recurrence risks despite surgery and therapy. This approval is a major step forward, offering renewed hope and improved outcomes for those affected by this devastating disease.”
Currently regulatory applications for the Imfinzi plus FLOT perioperative regimen are under review in the European Union and Japan, as well as in Australia, Canada, Switzerland, and several other countries, following the US FDA approval under Project Orbis.
References
FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma, US FDA, 25 November 2025, https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-resectable-gastric-or-gastroesophageal-junction-adenocarcinoma
Imfinzi approved in the US as first and only perioperative immunotherapy for patients with early gastric and gastroesophageal cancers, Astrazeneca, 25 November 2025, https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-approved-in-the-us-as-first-and-only-perioperative-immunotherapy-for-patients-with-early-gastric-and-gastroesophageal-cancers.html
Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer, ClinicalTrials.gov ID NCT04592913, https://clinicaltrials.gov/study/NCT04592913