FDA Approves Perioperative Durvalumab for Resectable Gastric/GEJ Adenocarcinoma

The FDA has approved durvalumab (Imfinzi) for use in combination with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) as neoadjuvant and adjuvant treatment, followed by single-agent durvalumab, for adult patients with resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma.1

The approval was supported by findings from the phase 3 MATTERHORN trial (NCT04592913), which demonstrated that treatment with durvalumab plus FLOT led to a 29% reduction in the risk of disease progression, recurrence, or death compared with FLOT alone (HR, 0.71; 95% CI, 0.58-0.86; P < .001).1,2 The median event-free survival (EFS) was not reached (95% CI, 40.7-not estimable [NE]) with durvalumab vs 32.8 months (95% CI, 27.9-NE) with FLOT alone.1 The 24-month EFS rates were 67.4% and 58.5%, respectively.2

Furthermore, data supporting the approval showed that the pathological complete response (pCR) rate was 19.2% (95% CI, 15.7%-23.0%) in the durvalumab arm vs 7.2% (95% CI, 5.0%-9.9%) in the FLOT alone arm (P < .001).1

Additional data reported from MATTERHORN showed the pathologic complete response (pCR) rate was 19.2% with durvalumab compared with 7.2% with FLOT alone (relative risk, 2.69; 95% CI, 1.86-3.90).

In the trial's final overall survival (OS) analysis, which was presented at the 2025 ESMO Congress, the median OS was not reached in both arms (HR, 0.78; 95% CI, 0.63–0.96; P =.021).3,4

How Was the MATTERHORN Trial Designed?

The global, randomized, double-blind, placebo-controlled phase 3 trial enrolled 948 patients with resectable gastric or GEJ adenocarcinoma that was stage II or higher. Patients were randomly assigned 1:1 to receive durvalumab at 1500 mg every 4 weeks (n = 474) or placebo (n = 474), both in combination with perioperative FLOT for 4 cycles. This was followed by adjuvant durvalumab or placebo plus FLOT for 2 cycles and durvalumab or placebo monotherapy for up to 10 cycles.5

The primary end point was EFS; secondary end points included OS and pCR rate.

What is the Safety Profile of Durvalumab Plus FLOT?

The safety of durvalumab plus FLOT was consistent with the known profiles of each agent. Grade 3/4 adverse effects occurred in 71.6% of patients in the durvalumab arm vs 71.2% in the placebo arm. Surgery was delayed in 10.1% and 10.8% of patients, respectively, and delays in initiating adjuvant therapy occurred in 2.3% and 4.6%.

References

1. FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma. 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
2. Janjigian Y, Al-Batran S-E, Wainberg Z, et al. Event-free survival (EFS) in MATTERHORN: a randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC). J Clin Oncol. 2025;43(suppl 17):LBA5. doi:10.1200/JCO.2025.43.17_suppl.LBA5
3. Tabernero, J, Al-Batran S-E, Wainberg ZAA, et al. Final overall survival (OS) and the association of pathological outcomes with event-free survival (EFS) in MATTERHORN: A randomised, phase III study of durvalumab (D) plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric/gastroesophageal junction (G / GEJ) adenocarcinoma. Presented at: ESMO 2025 Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA81.
4. Imfinzi. Prescribing information. Updated November 2025. Accessed December 1, 2025. https://drd9vrdh9yh09.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/9496217c-08b3-432b-ab4f-538d795820bd/9496217c-08b3-432b-ab4f-538d795820bd_viewable_rendition__v.pdf
5. Assessing durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer. ClinicalTrials.gov. Updated April 3, 2025. Accessed July 28, 2025. https://clinicaltrials.gov/study/NCT04592913