33Four-year survival and safety analysis from the Phase 3 TOPAZ-I study of durvalumab plus chemotherapy in biliary tract cancer
Aiwu Ruth He, Do-Youn Oh, Shukui Qin, Li-Tzong Chen, Takuji Okusaka, Arndt Vogel, Rebecca Griffin, Julie Wang, Ioannis Xynos, Juan W ValleAbstract
Background & Objectives
In the primary analysis of the TOPAZ-I study, durvalumab (D) + gemcitabine and cisplatin (GC) significantly improved overall survival (OS) vs placebo (PBO) + GC with manageable safety in participants (pts) with advanced biliary tract cancer (aBTC). This final post-hoc analysis evaluated 4-year OS and safety.
Method
Pts with aBTC received D or PBO + GC every 3 weeks followed by D or PBO monotherapy every 4 weeks. OS, exposure, adverse events (AEs) resulting in discontinuation, and serious AEs (SAEs) were assessed-48 months (mo) after the last pt was randomised (data cut-off: 28 Feb 2025).
Results
Overall, 685 pts were randomised to D + GC (n = 341) or PBO + GC (n = 344). The median (range) follow-up in censored pts was 56.9 (1.7-67.2) mo for pts receiving D + GC and 50.7 (0.9-62.6) mo for pts receiving PBO + GC. The median OS (95% Cl) was 13.0 (11.6-14.1) mo for D + GC and 11.4 (10.1-12.5) mo for PBO + GC (HR, 0.75; 95% CI, 0.6-0.9). The 48-mo OS rate was 11.8% for D + GC vs 4.3% for PBO + GC. Subsequent anticancer therapy use and study drug exposure are also reported (Table). Safety was consistent with prior analyses. The rate of SAEs possibly related to treatment was similar between arms. Since the 3-year analysis, no additional pts had AEs leading to discontinuation; 3 pts in the D + GC arm had additional SAEs unrelated to treatment.
Conclusion
This is the first randomised Phase 3 study reporting 4-year OS in aBTC with combined immunotherapy and chemotherapy. Consistent clinically meaningful long-tenn survival benefit was observed with D + GC. The safety profile remained manageable with no new safety signals. This further supports standard of care status for D + GC in pts with aBTC.