MATTERHORN Sets New Standard in Gastric Cancer

The phase III MATTERHORN trial (NCT04592913) has established a new standard of care for patients with resectable, locally advanced esophageal, gastroesophageal junction (GEJ), and gastric adenocarcinoma, according to Geoffrey Y. Ku, MD, a gastrointestinal medical oncologist and cellular therapist at Memorial Sloan Kettering Cancer Center.

In the video, Ku explains that MATTERHORN demonstrated that the addition of durvalumab, an anti–PD-L1 antibody, to perioperative chemotherapy with the FLOT regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel) significantly improved pathologic complete response (pCR) rates, event-free survival (EFS), and overall survival (OS) compared with perioperative FLOT alone.

Initial resultsshowing the pCRand EFS benefits were presented at the 2025 American Society of Clinical Oncology Annual Meeting. The median follow-up at this analysis was 31.6 months (range, 0.0-48.1) for the durvalumab arm (n = 474) and 31.4 months (range, 0.0-48.1) for the FLOT-alone arm (n = 474). The median EFS was not reached with the durvalumab-based regimen compared with 32.8 monthsin the control arm (HR, 0.71; 95% CI, 0.58-0.86; P <.001).The 18- and 24-month EFS rates were 73% vs 64% and 67% vs 59% in the 2 arms, respectively.

Subsequently, results presented at the 2025 European Society for Medical Oncology Congress definitively establishedthe OS benefit with the durvalumab regimen.The final OS analysis of the intention-to-treat population demonstrated an HR of 0.78 (95% CI, 0.63-0.96; P =.021) in the investigational arm vs the control arm, with median OS not reached in either arm.

Based on the MATTERHORN results, the durvalumab-FLOT combination received FDA approval in November 2025, a turnaround Ku describes as reshaping practice almost overnight.

Ku emphasizes that, absent clear contraindications to immunotherapy, any patient presenting with resectable, locally advanced esophageal, GEJ, or gastric adenocarcinoma should now receive durvalumab in combination with perioperative FLOT chemotherapy. With the perioperative backbone now in place, he expects ongoing and future trials to build the next generation of treatment strategies on top of it.