MATTERHORN Trial

The MATTERHORN trial was a global, Phase 3 study that investigated the addition of Durvalumab (an immunotherapy drug) to the standard FLOT chemotherapy regimen in patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. The trial aimed to evaluate whether this combination could improve survival outcomes and pathological responses.

Participants were randomized into two groups: one received Durvalumab (1500 mg) combined with FLOT chemotherapy, while the other received a placebo with FLOT. FLOT chemotherapy was administered every two weeks for 4 cycles before surgery (neoadjuvant) and 2 cycles after surgery (adjuvant). After surgery, patients continued with Durvalumab or placebo every 4 weeks for up to 10 additional cycles, extending the immunotherapy treatment.

The primary endpoint of the trial was Event-Free Survival (EFS), while secondary endpoints included pathological complete response (pCR), major pathological response (MPR), and Overall Survival (OS). PD-L1 expression (a biomarker) was also analyzed to assess its impact on treatment outcomes.

Results showed that the combination of Durvalumab + FLOT significantly improved OS, with a 22% reduction in the risk of death compared to placebo + FLOT. EFS also improved, particularly in patients achieving a pathological response. Additionally, nodal downstaging (reduction in cancer spread to lymph nodes) was more frequent in the Durvalumab group (58.2% vs 44.8%). Importantly, the survival benefits were consistent across both high and low PD-L1 expression groups.

The study concluded that Durvalumab + FLOT chemotherapy provides a meaningful survival benefit and may set a new standard of care for resectable gastric and GEJ adenocarcinomas.