Durvalumab plus FLOT improves event-free survival in gastric, GEJ adenocarcinoma

Patients with resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma demonstrate significant improvements in event-free survival (EFS) following treatment with durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy compared with placebo plus FLOT, as shown by the results of the phase III MATTERHORN study.

Furthermore, the treatment exhibited no significant differences in the main quality of life (QoL) scores and had a tolerable safety profile.

“MATTERHORN supports the positive benefit-risk profile of perioperative durvalumab with FLOT and its global adoption as a new standard for patients with localized gastric and GEJ adenocarcinoma,” said lead study author Dr Salah-Eddin Al-Batran, Krankenhaus Nordwest, University Cancer Center Frankfurt, and Frankfurt Institute of Clinical Cancer Research, Frankfurt, Germany.

Al-Batran and his team conducted this double-blind, global, phase III study in patients with resectable untreated gastric and GEJ adenocarcinoma. They randomly allocated the participants in a 1:1 ratio to receive either durvalumab 1,500 mg or placebo every 4 weeks (Q4W) with FLOT every 2 weeks (Q2W) for four cycles (two cycles each neoadjuvant/adjuvant), followed by durvalumab or placebo Q4W for 10 cycles. [ESMO GI 2025, abstract LBA4]

The primary outcome was EFS (time from randomization to progression, recurrence, or death), and EFS superiority for durvalumab with FLOT vs placebo with FLOT was assessed in all patients. Additionally, the research team evaluated patient-reported outcomes (PRO) by time to deterioration (TTD) using EORTC QLQ-30 in participants who completed questionnaires (PRO analysis set). Finally, they assessed adverse events (AEs) in the safety analysis set.

Survival benefit

Patients in the durvalumab plus FLOT group exhibited statistically significant improvements in EFS compared with placebo plus FLOT (hazard ratio [HR], 0.71, 95 percent confidence interval [CI], 0.58–0.86; p<0.001; median EFS not reached for durvalumab with FLOT vs 32.82 months for FLOT alone).

Likewise, the median overall survival (OS) was not reached for durvalumab with FLOT compared with 47.21 months for FLOT alone (HR, 0.78, 95 percent CI, 0.62–0.97; p=0.025; significance threshold p<0.0001). OS is set to be re-evaluated during the final analysis, according to the researchers.

“Durvalumab with FLOT significantly improved EFS vs FLOT alone in resectable gastric and GEJ adenocarcinoma,” said Al-Batran. “OS data were encouraging, [but] final OS analysis [is still] pending.”

Moreover, no significant between-group differences were observed in TTD of QoL assessed by EORTC QLQ-C30 (median QoL TTD 13.86, 95 percent CI, 11.24–19.98 for durvalumab with FLOT vs 13.60, 95 percent CI, 10.68–16.46 for placebo with FLOT). Maximum grade 3/4 AE rates were also comparable between the two treatment arms (71.6 percent vs 71.2 percent).

“The addition of durvalumab to perioperative FLOT resulted in no difference in overall health-related QoL, participant function, and symptom burden,” Al-Batran said.

“The results support durvalumab plus FLOT as a potential new global standard of care for resectable gastric and GEJ adenocarcinoma,” he added.

“Perioperative FLOT is standard of care for resectable gastric and GEJ adenocarcinoma,” Al-Batran said, “However, recurrence is common, and there is a need for better systemic disease control.”