Immune-mediated adverse events in MATTERHORN

In this video, Dr Filip Van Herpe discusses a poster presented at ESMO GI 2026 on immune-mediated adverse events (imAEs) in the phase III MATTERHORN study.¹ MATTERHORN evaluated perioperative FLOT chemotherapy with durvalumab versus FLOT with placebo in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma. The current analysis focused on the frequency and clinical impact of imAEs, and explored event-free survival according to whether or not patients experienced these events. 

As expected, imAEs were more frequent in the durvalumab plus FLOT arm than in the placebo plus FLOT arm. However, most events were grade 1 or 2, occurred during the adjuvant period, and were manageable according to standard treatment guidelines. Dr Van Herpe highlights that possible imAEs were also reported in the placebo arm, which reflects the challenges of assigning causality in a blinded trial. Importantly, the occurrence of imAEs did not appear to compromise the overall benefit of treatment. In the exploratory analysis, durvalumab plus FLOT improved event-free survival versus placebo plus FLOT both in patients with imAEs and in those without imAEs, including among patients who completed surgery. 

Overall, these findings suggest that the immune-mediated toxicity profile of durvalumab plus FLOT is manageable and should not discourage use of the regimen in appropriate patients.