FDA Approves Durvalumab Plus FLOT as Perioperative Therapy for Resectable Gastric and Gastroesophageal Junction Adenocarcinoma
Key Clinical Takeaways
- Design/Population: The phase 3 MATTERHORN trial enrolled 948 patients with stage II to IVA resectable gastric or gastroesophageal junction adenocarcinoma. Participants were randomized 1:1 to receive durvalumab plus FLOT or placebo plus FLOT in neoadjuvant and adjuvant phases, followed by durvalumab or placebo monotherapy.
- Key Outcomes: Durvalumab plus FLOT significantly improved event-free survival compared with chemotherapy alone (median EFS not reached vs 32.8 months; HR, 0.71; p < .001). The regimen also achieved a higher pathological complete response rate (19.2% vs 7.2%; p < .001) and a favorable trend in overall survival (HR, 0.78; p = .021).
- Safety: Safety results were consistent with previous durvalumab studies, with no unexpected adverse signals observed. The prescribing information includes warnings for immune-mediated events, infusion-related reactions, stem cell transplant complications, and embryo-fetal toxicity.
- Clinical Relevance: Durvalumab combined with FLOT represents a new standard of care for patients with resectable GC/GEJC, improving efficacy outcomes in both neoadjuvant and adjuvant settings. This marks the first immunotherapy-based perioperative regimen approved for this patient population.
On November 25, 2025, the US Food and Drug Administration (FDA) approved durvalumab in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as both neoadjuvant and adjuvant treatment, followed by single-agent durvalumab, for patients with resectable gastric or gastroesophageal junction adenocarcinoma. This approval was based on results from the phase 3 MATTERHORN trial.
In this double-blind, placebo-controlled study, 948 previously untreated patients were randomized 1:1 to receive either durvalumab or placebo plus FLOT. The primary end point was event-free survival (EFS), assessed by blinded independent central review. Key secondary end points included overall survival (OS) and pathological complete response (pCR).
At analysis, the median EFS was not reached in the durvalumab plus FLOT arm and was 32.8 months in the placebo plus FLOT arm (hazard ratio [HR], 0.71; 95% CI, 0.58 to 0.86; P < .001). The median OS was not reached in either treatment arm (HR, 0.78; 95% CI, 0.63 to 0.96; P = .021). The pCR rate was 19.2% in the durvalumab plus FLOT arm and 7.2% in the placebo plus FLOT arm (P < .001).
The recommended durvalumab dose for patients weighing ≥30 kg is 1500 mg every 4 weeks with chemotherapy for up to 4 cycles (neoadjuvant and adjuvant), followed by 1500 mg every 4 weeks for up to 10 additional cycles (adjuvant). For patients weighing <30 kg, the recommended dose is 20 mg/kg every 4 weeks with chemotherapy for up to 4 cycles, followed by 20 mg/kg every 4 weeks for up to 10 additional cycles (adjuvant). Treatment may continue until disease progression, recurrence, unacceptable toxicity, or completion of a maximum of 12 cycles after surgery.
The prescribing information includes safety warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem-cell transplantation, and embryo-fetal toxicity.
Source:
US Food and Drug Administration. Accessed on November 25, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-resectable-gastric-or-gastroesophageal-junction-adenocarcinoma
