Durvalumab plus FLOT improves survival in Asians with G/GEJ adenocarcinoma

Adding durvalumab to 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) improves event-free survival (EFS) and overall survival (OS) in Asian patients with resectable gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, according to a subgroup analysis of the phase III MATTERHORN trial presented at ESMO Asia 2025.

At follow-up, the median EFS and OS were not reached in both treatment arms, with a hazard ratio (HR) of 0.74 for both endpoints. [ESMO Asia 2025, abstract 2700]

The durvalumab plus FLOT arm also demonstrated higher EFS rates at 24 months (72 percent vs 64 percent) and OS rates at both 24 (81 percent vs 78 percent) and 36 months (76 percent vs 72 percent) than the placebo plus FLOT arm.

Additionally, patients in the combination arm achieved a higher pathological complete response (pCR) rate of 19 percent compared with 6 percent in the placebo plus FLOT arm, corresponding to a treatment difference of 13 percent (odds ratio, 3.96).

The EFS and OS benefits, as well as pCR rates, observed with the combination regimen of durvalumab and FLOT in the Asian subgroup were consistent with that observed in the global ITT population, said lead author Dr Yelena Janjigian from Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine in New York, US.

Safety

The rates of grade 3/4 adverse events (AEs) were similar between the durvalumab plus FLOT and FLOT alone arms in the Asian subgroup (88 percent for both), which were similar to that observed in the global population (72 percent vs 71 percent).

Neutropenia (69 percent for both), decreased white blood cell count (24 percent vs 18 percent), and febrile neutropenia (12 percent vs 9 percent) were the most frequently reported grade 3/4 AEs in both the durvalumab plus FLOT and placebo plus FLOT arms.

“Durvalumab plus FLOT showed a manageable safety profile in the Asian subgroup,” Janjigian noted.

New standard of care?

This subgroup analysis involved 180 Asian patients (enrolled from Japan, Republic of Korea, Taiwan) with resectable G/GEJ adenocarcinoma. Participants were randomized in a 1:1 ratio to receive two doses of durvalumab 1,500 mg or placebo Q4W (day 1 of each cycle; n=90 in each group) plus four doses of FLOT* Q2W (days 1 and 15 of each cycle) preoperatively and postoperatively, followed by 10 doses of postoperative durvalumab or placebo monotherapy.

Overall, “the addition of durvalumab to FLOT improved EFS, OS, and pCR rates vs placebo in Asian participants with resectable G/GEJ adenocarcinoma,” Janjigian concluded.

“MATTERHORN results support perioperative durvalumab plus FLOT as a new standard of care for patients with localized G/GEJ adenocarcinoma in Asia and globally,” she added.