According to the MATTERHORN study, there was a statistically significant and clinically meaningful improvement in event-free survival (EFS) seen with durvalumab plus FLOT chemotherapy compared to placebo plus 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) among patients with resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.

These data were first presented by Salah-Eddin Al-Batran, MD, Institute of clinical Cancer Research, Frankfurt, Germany, at the 2025 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Annual Congress in Barcelona, Spain.

The global, double-blind, phase 3 MATTERHORN study randomized untreated patients with resectable G/GEJ adenocarcinoma to receive either durvalumab (n = 474) or placebo (n = 474), plus FLOT chemotherapy. Patients received 1500 mg of durvalumab or placebo every 4 weeks plus FLOT every 2 weeks for 4 cycles, followed by durvalumab or placebo for 10 cycles. The primary end point of this study was EFS, with overall survival (OS) as a key secondary end point. Additional end points included patient-reported outcomes and adverse events rates, from the second pre-planned interim analysis.

There was a statistically significant improvement of EFS seen with durvalumab plus FLOT, with a median EFS that was not reached in the durvalumab arm and a median EFS of 32.82 months in the placebo arm (hazard ratio [HR], 0.71; P < .001). The median OS was not reached for the durvalumab arm vs 47.21 months for the placebo arm. No relevant differences were seen between the arms in the time to deterioration of quality of life, as assessed by EORTC QLQ-C30. The maximum grade 3/4 adverse event rates were 71.6% in the durvalumab arm and 71.2% in the placebo arm. 

Study authors concluded, “The results support [durvalumab plus FLOT] as a potential new global standard of care for resectable G/GEJ adenocarcinoma. 

Source:

Al-Batran S-E, Wainberg ZA, Muro K, et al. Event-free survival and patient-reported outcomes (PROs) in MATTERHORN: A randomised, phase III study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) chemotherapy in resectable gastric/gastroesophageal junction adenocarcinoma. Presented at 2025 ESMO GI Cancers Annual Congress. July 2-5, 2025; Barcelona, Spain. Abstract: LBA4