FDA Approves Durvalumab With FLOT Chemotherapy for Resectable Gastric and Gastroesophageal Junction Cancer

Today, the FDA approved durvalumab (Imfinzi; AstraZeneca) in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy as a neoadjuvant and adjuvant treatment, followed by single-agent durvalumab, for adults with resectable, early-stage, or locally advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC), making it the first perioperative immunotherapy for patients with early gastric and gastroesophageal cancers.¹

For patients weighing 30 kg or more, the recommended dose is 1500 mg every 4 weeks, administered in combination with FLOT chemotherapy for up to 4 cycles (neoadjuvant and adjuvant treatment), followed by 1500 mg as a single agent every 4 weeks for up to 10 cycles (adjuvant treatment).² Patients weighing less than 30 kg should receive 20 mg/kg every 4 weeks with FLOT chemotherapy for up to 4 cycles (neoadjuvant and adjuvant treatment), followed by 20 mg/kg as a single agent every 4 weeks for up to 10 cycles (adjuvant treatment).

Treatment should continue until disease progression, recurrence, unacceptable toxicity, or a maximum of 12 cycles post-surgery, whichever occurs first.

"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," Dave Fredrickson, executive vice president of AstraZeneca's oncology hematology business unit, said in a news release.¹ "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.”

MATTERHORN Trial Demonstrates Improved Survival, Pathological Response With Durvalumab

This approval is based on the phase 3 MATTERHORN trial (NCT04592913), whose results were presented this past summer at the 2025 American Society of Clinical Oncology Annual Meeting.³ The double-blind, placebo-controlled multicenter study randomized participants with resectable GC/GEJC 1:1 to receive either 1500 mg of durvalumab or placebo every 4 weeks plus FLOT for 4 cycles, followed by durvalumab or placebo every 4 weeks for 10 cycles.⁴ The primary end point was event-free survival, with secondary end points of overall survival and pathological complete response.

The study population consisted of 948 patients, half of whom received durvalumab (n = 474) and the other half (n = 474) received a placebo. Median follow-up was 31.5 (IQR, 26.7-36.6) months.

Two-year event-free survival was 67.4% among patients in the durvalumab group and 58.5% in the placebo group (HR, 0.71; 95% CI, 0.58-0.86; P < .001). Additionally, 2-year overall survival was 75.7% in the durvalumab group and 70.4% in the placebo group (HR for months 0-12, 0.99 [95% CI, 0.70-1.39]; HR from month 12 onward, 0.67 [95% CI, 0.50-0.90]; P = .03).

The researchers also determined that 19.2% of patients in the durvalumab group had a pathological complete response vs 7.2% in the placebo group (relative risk, 2.69; 95% CI, 1.86-3.90). Regarding safety, adverse events with a maximum grade of 3 or 4 were reported in 71.6% (n = 340) of the durvalumab group and 71.2% (n = 334) of the placebo group.

“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," Yelena Y. Janjigian, MD, principal investigator in the MATTERHORN trial, said in a news release.¹ "Nearly 7 in 10 patients were alive at 3 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.”

References

1. 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
2. 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
3. Caffrey M. Adding perioperative durvalumab to chemo combo boosts EFS, overall survival in patients with gastric, GEJ cancer. AJMC^®. June 1, 2025. Accessed November 25, 2025. https://www.ajmc.com/view/adding-perioperative-durvalumab-to-chemo-combo-boosts-efs-overall-survival-in-patients-with-gastric-gej-cancer
4. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. N Engl J Med. 2025;393(3):217-230. doi:10.1056/nejmoa2503701