Immune-mediated adverse events in the randomized phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer

Introduction: We assessed immune-mediated adverse events (imAEs) in the TOPAZ-1 (NCT03875235) study of durvalumab plus gemcitabine and cisplatin (GemCis) in advanced biliary tract cancer (aBTC). Methods: Participants were randomized 1:1 to durvalumab (1500 mg) or placebo, plus GemCis (gemcitabine [1000 mg/m2] and cisplatin [25 mg/m2]) intravenously, followed by durvalumab (1500 mg) or placebo Q4W. We assessed imAE incidence, time to onset (TTO), and association with overall survival (OS). Results: In durvalumab (n = 338) versus placebo (n = 342), imAEs were reported in 13.9% versus 4.7% of participants, with median TTO of 127.0 versus 86.5 days, respectively. OS HR for durvalumab versus placebo in participants with imAEs was 0.59 (95% CI, 0.30-1.23) and was 0.83 (95% CI, 0.70-1.00) in participants without imAEs. Conclusions: Durvalumab demonstrated an OS benefit versus placebo in aBTC, irrespective of imAEs, which were mostly low grade and manageable. The results in these subgroups were consistent with the overall primary analysis. Trial registration: ClinicalTrials.gov NCT03875235