MATTERHORN: Durvalumab Plus FLOT Improves Overall Survival in Resectable Gastric and GEJ Adenocarcinoma
Key Insights
Final MATTERHORN analysis showed perioperative durvalumab plus FLOT (search) significantly improved overall survival versus placebo plus FLOT, with an HR of 0.78 (95% CI 0.63-0.96; p=0.021).
At 24 and 36 months, overall survival rates were 76% versus 70% and 69% versus 62% for durvalumab plus FLOT (search) versus placebo plus FLOT, respectively.
Central pathology review found pathological complete response in 24% versus 9% of surgical patients, and 58% versus 45% had no nodal involvement at surgery.
The phase 3 MATTERHORN trial's final overall survival analysis, published in The Lancet, shows that adding perioperative durvalumab to FLOT (search) significantly improved overall survival in adults with previously untreated, histologically confirmed stage II-IVa resectable gastric or gastroesophageal junction adenocarcinoma (search). In the 948 randomized patients (474 per arm), 160 deaths occurred in the durvalumab group versus 192 in the placebo group, yielding an HR of 0.78 (95% CI 0.63-0.96; p=0.021). Median overall survival was not reached in either group; 24-month rates were 76% versus 70% and 36-month rates were 69% versus 62%.
Pathological and surgical outcomes also favored durvalumab plus FLOT (search). Among patients with centrally evaluable specimens, pathological complete response occurred in 24% versus 9%, major pathological response in 33% versus 18%, and any pathological response in 90% versus 84%. Event-free survival numerically favored durvalumab across response categories, with HRs of 0.29 for pathological complete response, 0.32 for major pathological response, and 0.60 for any pathological response. No nodal involvement at surgery was seen in 58% versus 45% of evaluable patients, and downstaging to node-negative disease occurred in 36% versus 28%.
Safety remained consistent with prior MATTERHORN reporting: grade 3 or 4 adverse events occurred in 72% versus 71% of patients, serious adverse events in 48% versus 44%, and immune-mediated adverse events of any grade in 23% versus 7%. Adverse events led to discontinuation of any trial treatment in 30% versus 23%. Surgical feasibility was not compromised, with complete resection achieved in 92% of both groups. The authors noted that pathological response and nodal analyses were post-hoc and exploratory, and that diffuse histology was not centrally confirmed.