Durvalumab Receives FDA Approval for Resectable Gastric or Gastroesophageal Junction Adenocarcinoma

The FDA approved durvalumab (Imfinzi; AstraZeneca) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy as neoadjuvant and adjuvant treatment, followed by a single agent (durvalumab) to treat adults with respectable, early-stage, and locally advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).¹

“This approval ushers in a new clinical paradigm for patients with early gastric and gastroesophageal junction cancers, with [durvalumab] plus FLOT delivering a durable survival benefit that increases over time. As the third US approval for a perioperative [durvalumab]-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,” Dave Fredrickson, executive vice president, oncology hematology business unit, AstraZeneca, said in a news release.²

What Is the Role of Durvalumab?

As a human monoclonal antibody, durvalumab binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins. With this, the treatment counters the tumor’s immune-evading tactics and releases the inhibition of immune responses.²

For patients weighing 30 kg or more, the recommended durvalumab dose is 1500 mg every 4 weeks with chemotherapy for up to 4 cycles, followed by 1500 mg alone every 4 weeks for up to 10 additional cycles. For patients under 30 kg, the dose is 20 mg/kg every 4 weeks with chemotherapy for up to 4 cycles, then 20 mg/kg alone every 4 weeks for up to 10 cycles. Treatment is also recommended to continue until disease progression, recurrence, unacceptable toxicity, or completion of 12 post-surgery cycles.^1,2

Clinical Trial Results Supporting Durvalumab's Approval

The approval of durvalumab in combination with FLOT is supported by data from the randomized, double-blind, placebo-controlled, multicenter MATTERHORN (NCT04592913) trial. The study evaluated the safety and efficacy of the treatment in a total of 948 patients with previously untreated and resectable GC/GEJC that were randomly assigned 1:1 to receive durvalumab and FLOT or placebo and FLOT.^1,2,4

Interim results demonstrated that the durvalumab-based perioperative regimen reduced the risk of disease progression, recurrence, or death by 29% and resulted in higher 12- and 24-month event-free survival rates compared with chemotherapy alone. Final data showed a 22% reduction in the risk of death and improved 3-year survival with durvalumab plus FLOT, with continued and consistent benefits regardless of PD-L1 status.^1,2

“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.” 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 in the news release.²

The safety of durvalumab and FLOT was similar to known safety profiles for each medicine. Additionally, grade 3 or higher adverse events due to any cause were similar between the durvalumab with FLOT arm and the FLOT-only arm.²

“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,” Janjigian said.²

What Are Gastric and Gastroesophageal Junction Cancers?

GC is the fifth most common cancer globally and the fifth leading cause of cancer mortality. In 2022, almost 1 million new patients were diagnosed with GC, accounting for nearly 660,000 global deaths.¹

GC does not always cause symptoms early on, but when it does, individuals could experience trouble swallowing, belly pain, heartburn, indigestion, nausea, vomiting, and a feeling of fullness or bloating after eating even small amounts. Some individuals may lose their appetite, lose weight without trying, or feel extreme tiredness. In more advanced cases, stools may appear black, and symptoms often become more noticeable only once the cancer has progressed.³

In the US, GC usually starts by the gastroesophageal junction. GEJC is a type of gastric cancer that begins and spans the area where the esophagus connects to the stomach.^1,3

“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,” Aki Smith, founder and executive director of Hope for Stomach Cancer, said in the news release.²

REFERENCES

1. FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma. News release. FDA. November 25, 2025. Accessed November 25, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-resectable-gastric-or-gastroesophageal-junction-adenocarcinoma?utm_medium=email&utm_source=govdelivery

2. Imfinzi approved in the US as first and only perioperative immunotherapy for patients with early gastric and gastroesophageal cancers. News release. AstraZeneca. November 25, 2025. Accessed November 25, 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

3. Mayo Clinic Staff. Stomach cancer. News release. Mayo Clinic. June 19, 2024. Accessed November 25, 2025. https://www.mayoclinic.org/diseases-conditions/stomach-cancer/symptoms-causes/syc-20352438

4. Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer. Updated April 3, 2025. Accessed November 25, 2025. https://clinicaltrials.gov/study/NCT04592913