Regional subgroup analysis of the phase 3 TOPAZ-1 study of durvalumab (D) plus gemcitabine and cisplatin (GC) in advanced biliary tract cancer (BTC).

Abstract

4075 Background: TOPAZ-1 (NCT03875235) is a randomized, double-blind, global, Phase 3 study evaluating the efficacy and safety of D + GC as first-line treatment for patients (pts) with advanced BTC. D + GC significantly improved overall survival (OS) versus placebo (PBO) + GC (Oh D-Y, et al. J Clin Oncol 2022;40[suppl 4]. Abs 378). Methods: A pre-specified subgroup analysis was performed for efficacy outcomes including OS for pts enrolled in Asia (China, Hong Kong, India, Japan, South Korea, Taiwan, Thailand) or the rest of the world (RoW; Europe [Bulgaria, France, Italy, Poland, Russia, Turkey, United Kingdom], North America [NA; USA], and South America [SA; Argentina, Chile]). Post hoc country level analyses were also performed to better characterize outcomes in different countries and regions. Pts with BTC were randomized 1:1 to D (1500 mg once every 3 weeks [Q3W]) or PBO, + G (1000 mg/m2) and C (25 mg/m2) on Days 1 and 8, Q3W, for up to 8 cycles, followed by D (1500 mg Q4W) or PBO monotherapy until disease progression or unacceptable toxicity. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from a Cox proportional hazards model. Results: Pt numbers were balanced across regions (Asia, n=374 [54.6%]; RoW, n=311 [45.4%]). Baseline characteristics were balanced between regions with the exception of modest differences in important pre-defined prognostic factors, including disease status: recurrent disease (Asia 23%; RoW 14.5%), ECOG performance status 1 (Asia 59.1%; RoW 41.2%), and metastatic disease (Asia 89.3%; RoW 82%). In the PBO arm, more pts in Asia received subsequent anti-cancer therapies than pts in RoW (53.6% vs 43.9%). Median duration of follow-up in censored pts was about 2 months (mo) longer in Asia versus RoW (14.8 vs 13.0 mo in D + GC; 13.8 vs 12.1 mo in PBO + GC). Regional level analysis (Table) showed outcomes were similar and approximated the overall population for Asia, Europe, and NA. Grade 3/4 adverse events were similar for Asia (D + GC 78.5%; PBO + GC 78.6%) and RoW (D + GC 72.7%; PBO + GC 76.7%). Conclusions: Despite some regional differences in prognostic characteristics, OS trends favored D + GC versus PBO + GC for pts enrolled in both Asia and RoW, supporting the use of D + GC as a potential new treatment option for all pts with BTC. Country-specific and regional outcomes continue to be explored. Clinical trial information: NCT03875235. [Table: see text]