Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study

Background & Aims: At the TOPAZ-1 (NCT03875235) primary analysis, durvalumab plus gemcitabine and cisplatin (GemCis) significantly improved overall survival (OS) in advanced biliary tract cancer (aBTC). We report updated exploratory analyses of OS and safety, extended long-term survivors (eLTS), and subsequent anticancer therapy use. Methods: Participants with aBTC received durvalumab+GemCis or placebo+GemCis every 3 weeks (≤8 cycles), then durvalumab or placebo monotherapy every 4 weeks until progressive disease or other discontinuation criteria were met. OS and serious adverse events were assessed in the full analysis and safety analysis sets, respectively. eLTS outcomes were assessed (full analysis set participants alive ≥30 months after randomisation). Results: A total of 685 participants were randomised: durvalumab+GemCis (n = 341); placebo+GemCis (n = 344). After a median 41.3 (95% CI 39.3–44.1) months’ follow-up in all participants, median OS (95% CI) for durvalumab+GemCis vs. placebo+GemCis was 12.9 (11.6–14.1) vs. 11.3 (10.1–12.5) months (hazard ratio, 0.74 [95% CI 0.63–0.87]); 36-month OS rate was 14.6% vs. 6.9%, respectively. In participants who achieved disease control (566/685; 82.6%), the 36-month OS rate was higher for durvalumab+GemCis (17.0%) vs. placebo+GemCis (7.6%). Overall, 12.8% were eLTS, with more eLTS in the durvalumab+GemCis (17.0%) vs. placebo+GemCis (8.7%) arms; eLTS included all clinically relevant subgroups. Durvalumab+GemCis improved OS regardless of subsequent anticancer therapy use. In eLTS, serious adverse events were comparable between arms and less frequent than in the full safety analysis set. Conclusions: Survival benefit and manageable safety continued with durvalumab+GemCis vs. placebo+GemCis approximately 3 years after the last participant was randomised. All clinically relevant subgroups were represented in eLTS, supporting standard-of-care status for durvalumab+GemCis in aBTC. Impact and implications: Durvalumab plus gemcitabine and cisplatin (GemCis) was approved for use in advanced biliary tract cancer (aBTC) after the primary analysis of the randomised, double-blind, phase III TOPAZ-1 study demonstrated that it significantly improved overall survival (OS) vs. placebo plus GemCis. This update, with analyses of OS and safety, extended long-term survivors, and subsequent anticancer therapy use, took place at a median follow-up of 41.3 months, which, to our knowledge, represents the longest follow-up to date in participants with aBTC. Survival benefit and manageable safety continued with durvalumab plus GemCis, all clinically relevant subgroups were represented in extended long-term survivors, and OS benefit with durvalumab plus GemCis was consistent regardless of subsequent anticancer therapy use. These long-term follow-up results support the standard-of-care status for durvalumab plus GemCis in aBTC, and enable physicians, patients and caregivers to make informed treatment decisions. Clinical trial registration: ClinicalTrials.gov Identifier: NCT03875235; https://clinicaltrials.gov/study/NCT03875235.