Dr Janjigian on the Efficacy of Durvalumab Plus Chemotherapy in Resectable GEJ Adenocarcinoma

"MATTERHORN showed for the first time in this disease that we can use immune checkpoint blockade in the perioperative setting, [and achieve] significantly improved EFS vs FLOT alone in resectable GEJ adenocarcinoma. This is an important step forward."

Yelena Y. Janjigian, MD, chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center, discussed results from the phase 3 MATTERHORN trial (NCT04592913), which evaluated perioperative durvalumab (Imfinzi) plus FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) vs placebo plus FLOT in patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Data presented during the 2025 ASCO Annual Meeting demonstrated that the addition of durvalumab to FLOT significantly improved event-free survival (EFS) compared with placebo plus FLOT. Among patients who received durvalumab plus FLOT (n = 474), the median EFS was not reached (NR; 95% CI, 40.7-NR), compared with 32.8 months (95% CI, 27.9-NR) for those who received placebo plus FLOT (n = 474; HR, 0.71; 95% CI, 0.58-0.86; log-rank P < .001). According to Janjigian, these findings reinforce the position of FLOT as the preferred systemic chemotherapy backbone and highlight the feasibility and efficacy of incorporating immune checkpoint blockade into the perioperative setting.

The trial included secondary end points of overall survival (OS), pathologic complete response, and disease-free survival. Although OS data remain immature, early trends appear favorable, and the final analysis is pending. Importantly, the EFS benefit was consistent across predefined subgroups and geographic regions, including Asia, North and South America, and Europe. No new safety concerns were identified, underscoring the regimen’s tolerability in a globally diverse patient population.

Janjigian emphasized that MATTERHORN is the first global, randomized study to demonstrate that an immune checkpoint inhibitor can be safely and effectively integrated into the neoadjuvant and perioperative treatment of resectable gastric/GEJ adenocarcinoma. Based on these data, she stated that the addition of durvalumab to FLOT may represent a new global standard of care for patients with localized disease, offering a clinically meaningful advance in a setting where curative-intent strategies are critically needed.