FDA Approves Neo/Adjuvant Durvalumab Combo in Gastric/GEJ Adenocarcinoma

The FDA has approved the combination of durvalumab (Imfinzi) plus FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) followed by durvalumab monotherapy for the neoadjuvant and adjuvant treatment of patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJ).¹

The safety and efficacy of durvalumab in this setting was evaluated in the randomized, double-blind, placebo-controlled, multicenter phase 3 MATTERHORN trial (NCT04592913). Patients in the durvalumab arm had a 29% reduction in the risk of cancer event or death compared with the placebo arm.

Median event-free survival (EFS), primary efficacy outcome measured, was not reached (NR; 95% CI, 40.7 months-not estimable [NE]) in the durvalumab arm compared with 32.8 months (95% CI, 27.9-NE) in the placebo arm (hazard ratio [HR], 0.71; 95% CI, 0.58-0.86; P <.001).

Median overall survival (OS), an additional efficacy outcome measured, was not reached (NR) in either arm (HR, 0.78; 95% CI, 0.63-0.96; P = .021). Further, pathologic complete response (pCR), another additional efficacy outcome measured in MATTERHORN, was 19.2% (95% CI, 15.723.0) in the durvalumab arm vs 7.2% (95% CI, 5.0-9.9; P <.001) in the placebo arm.

Patients evaluated (n = 948) had previously untreated and resectable stage II to stage IVA GC/GEJ were randomized 1:1 to receive either durvalumab and FLOT or a placebo and FLOT.

Durvalumab Combination Dosing Information in GC/GEJ?

For patients with a body weight of at least 30 kg, the recommended dose is 1500 mg every 4 weeks with chemotherapy for up to 4 cycles, in the neoadjuvant and adjuvant treatment settings, followed by 1500 mg of durvalumab monotherapy every 4 weeks for up to 10 cycles in the adjuvant setting.

The recommended dose for patients with a body weight below 30 kg is 20 m/kg of durvalumab every 4 weeks for up to 4 cycles in neoadjuvant and adjuvant settings, followed by 20 mg/kg of single-agent durvalumab every 4 weeks for up to 10 cycles in the adjuvant setting.

MATTERHORN Data Shared at ASCO

MATTERHORN OS data had a data cutoff of September 1, 2025, and findings from a final OS analysis were shared at the 2025 American Society of Clinical Oncology Annual Meeting.²

A survival analysis stratified by demographic and clinical characteristics demonstrated an improved OS in most key subgroups, and similar OS improvements were observed regardless of PD-L1 status. Patients with PD-L1-positive disease (PD-L1 TAP ≥1%) had an OS HR of 0.79 (95% CI, 0.63–0.99), and those with PD-L1-negative disease (PD-L1 TAP <1%) had an OS HR of 0.79 (95% CI, 0.41–1.50).

“The overall survival results of the MATTERHORN study strongly support the use of durvalumab plus chemotherapy with FLOT as a new global standard of care for patients with localized, [resectable, G/GEJ] adenocarcinoma,” said Josep Tabernero, MD, PhD, professor of medicine, head, Department of Medical Oncology, Vall d’Hebron University Hospital, and director of Vall d’Hebron Institute of Oncology, Barcelona, Spain, in his presentation.

Expert Nurse Advice on Treatment With Durvalumab

Abigail T. Ramontal, NHP, MSN, APRN-FP-C, provided nursing insights on the use of durvalumab to treat patients with endometrial cancer in an Rx Road Map guide for Oncology Nursing News.

She explained that durvalumab is a human monoclonal antibody that binds to programmed cell death ligand-1 (PD-L1) and prevents it from interacting with the programmed death receptor-1 (PD-1) and CD80 receptors, resulting in an antitumor response. Blocking this binding boosts the body’s immune system response against cancer cells.

For more information on the administration and management of durvalumab from Ramontal, read the full Rx Road Map here.

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. Tabernero, J. 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