Should We Add Durvalumab to Perioperative FLOT for Gastric and Gastroesophageal Cancer?

For patients with resectable gastric cancer, perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is the standard of care. Given that immune checkpoint inhibitors improve metastatic gastric cancer outcomes after chemotherapy, researchers are studying these agents as add-ons to perioperative chemotherapy in the curative setting. Investigators now report results from the industry-sponsored, double-blind, placebo-controlled, randomized, multinational phase 3 MATTERHORN trial. Participants received neoadjuvant durvalumab (or placebo) plus perioperative FLOT, surgery, and additional, adjuvant durvalumab (or placebo) to complete 1 year of therapy. Around 950 patients with gastric (68%) or gastroesophageal junction (33%) primary adenocarcinomas underwent surgery and were included in the study. Of these, 66% had a primary tumor stage of T3 and 25% T4, and 90% tested positive for PD-L1 expression.

The results:

• Durvalumab-FLOT (D-FLOT) significantly increased event-free survival (the primary endpoint) (67%) compared with FLOT alone (59%) at 24 months.
• The secondary endpoint of overall survival at 24 months also was significantly better with D-FLOT, 76%, over FLOT, 70%.
• Pathologic complete response also was more common with D-FLOT (19%) compared with FLOT (7%).
• The two treatment groups had similar rates of R0 resection, completion of therapy before and after surgery, and grade 3 or 4 treatment-related adverse events (72 with both treatments).