56P Updated overall survival (OS) from the phase III TOPAZ-1 study of durvalumab (D) or placebo (PBO) plus gemcitabine and cisplatin (+ GC) in patients (pts) with advanced biliary tract cancer (BTC)

Advanced BTC is a rare, heterogenous cancer with poor prognosis. At the preplanned interim analysis (data cutoff 11 August 2021) of TOPAZ-1 (NCT03875235), D + GC significantly improved OS versus PBO + GC in pts with advanced BTC (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.66–0.97; p=0.021). We report an updated OS and safety analysis for TOPAZ-1. Pts previously untreated for unresectable locally advanced, recurrent, or metastatic BTC were randomised 1:1 to receive D (1500 mg 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. The primary objective was to assess OS. This OS and safety analysis was conducted after 6 months (mo) of additional follow-up with 76.9% overall OS event maturity. At data cutoff (25 February 2022), 685 pts were randomised to D + GC (n=341) or PBO + GC (n=344); median (95% CI) follow-up time was 23.4 (20.6–25.2) mo and 22.4 (21.4–23.8) mo, respectively. Median (95% CI) OS was 12.9 (11.6–14.1) mo with D + GC and 11.3 (10.1–12.5) mo with PBO + GC (HR, 0.76; 95% CI, 0.64–0.91). OS HRs (95% CI) favoured D + GC in all prespecified subgroups, including disease status (initially unresectable, 0.79 [0.65–0.95]; recurrent, 0.76 [0.49–1.20]), primary tumour location (intrahepatic cholangiocarcinoma, 0.78 [0.62–0.99]; extrahepatic cholangiocarcinoma, 0.61 [0.41–0.91]; gallbladder cancer, 0.90 [0.64–1.25]) and PD-L1 (tumour area positivity [TAP] ≥1%, 0.75 [0.60–0.93]; TAP <1%, 0.79 [0.58–1.09]). OS rates (D + GC vs PBO + GC) at 12 mo, 18 mo and 24 mo were 54.3% vs 47.1%, 34.8% vs 24.1% and 23.6% vs 11.5%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 60.9% of pts receiving D and 63.5% of pts receiving PBO; TRAEs leading to discontinuation of any study medication occurred in 8.9% and 11.4% of pts, respectively. D + GC continues to demonstrate clinically meaningful benefit vs PBO, that is consistent among subgroups, and manageable safety with longer follow-up, further supporting D + GC as a new first-line standard of care regimen for pts with advanced BTC.