MATTERHORN—the new perioperative standard for resectable gastric and gastroesophageal junction cancer

Summary Positive results of the FLOT4-AIO trial in 2019 have established perioperative chemotherapy with FLOT (5-fluorouracil [5-FU], oxaliplatin, and docetaxel) as the standard approach for resectable adenocarcinoma of the stomach and gastroesophageal junction. Despite the improvement of clinical outcome when compared to the former anthracycline-based triplet chemotherapy, more than half of patients experience disease relapse and/or death with perioperative FLOT during follow-up. While the phase 3 KEYNOTE-585 trial—investigating the addition of pembrolizumab to the chemotherapy backbone cisplatin +5-FU/capecitabine—was a negative trial, the phase 3 MATTERHORN trial demonstrated superiority of FLOT combined with durvalumab (D-FLOT) compared to FLOT alone in terms of improved event-free survival (EFS) and overall survival (OS) and established D‑FLOT as the new standard of care for all-comers. Preliminary results of the ongoing DANTE phase 3 trial corroborate higher pathological complete remission (pCR) rates by combining perioperative FLOT + immune checkpoint blockade; however, EFS and OS results are pending. In light of the encouraging pCR rates achieved by the addition of pembrolizumab and trastuzumab to FLOT in HER2+ disease in the single-arm PHERFLOT phase 2 trial, the use of additional trastuzumab in this subgroup warrants further investigation.