Additional 6-Month Follow-up from the TOPAZ-1 Study Comparing Durvalumab with Placebo plus Gem/Cis in Patients with Advanced BTC

Web Exclusives — November 15, 2022

The phase 3 TOPAZ-1 study was a placebo-controlled study designed to evaluate durvalumab (D) plus gemcitabine/cisplatin (GemCis) for the treatment of advanced biliary tract cancer (BTC). Interim results suggested that D plus GemCis significantly improved overall survival (OS) in these patients compared with placebo (PBO) plus GemCis.1 The data reported here provide updated OS and safety analyses for the TOPAZ-1 study after an additional 6 months of follow-up.

Patients randomly assigned (1:1) in TOPAZ-1 were previously untreated for unresectable locally advanced, recurrent, or metastatic BTC. They received either D (1500 mg every 3 weeks) or PBO, as well as GemCis (1000 mg/m2 and 25 mg/m2, respectively) on days 1 and 8 every 3 weeks for a maximum of 8 cycles, followed by D (1500 mg every 4 weeks) or PBO monotherapy until disease progression or unacceptable toxicity. OS was evaluated for the entire patient population as well as several subgroups.

Median follow-up times were 23.4 months (95% confidence interval [CI], 20.6-25.2) for the D plus GemCis arm (n = 341) and 22.4 months (95% CI, 21.4-23.8) for the PBO plus GemCis arm. For the D plus GemCis group, median OS was 12.9 months (95% CI, 11.6-14.1), and 11.3 months (95% CI, 10.1-12.5) for the PBO plus GemCis group (hazard ratio [HR], 0.76; 95% CI, 0.64-0.91). When OS HRs were evaluated for prespecified subgroups, including disease status, primary tumor location, and PD-L1, all favored D plus GemCis. For disease status, OS HRs were 0.79 (95% CI, 0.65-0.95) and 0.76 (95% CI, 0.49-1.20) for initially resectable and recurrent, respectively. For primary tumor location, the OS HR for intrahepatic cholangiocarcinoma was 0.78 (95% CI, 0.62-0.99), the OS HR for extrahepatic cholangiocarcinoma was 0.61 (95% CI, 0.41-0.91), and the OS HR for gallbladder cancer was 0.90 (95% CI, 0.64-1.25). With regard to PD-L1, OS HRs were 0.75 (95% CI, 0.60-0.93) and 0.79 (95% CI, 0.58-1.09) for tumor area positivity (TAP) ≥1% and TAP <1%, respectively. OS rates for D plus GemCis versus PBO plus GemCis were as follows: 54.3% versus 47.1% at 12 months, 34.8% versus 24.1% at 18 months, and 23.6% versus 11.5% at 24 months. In addition, a higher proportion of patients responded to D plus GemCis versus PBO plus GemCis (26.7% vs 18.7%).

In the D plus GemCis arm, 60.9% of patients experienced grade 3/4 treatment-related adverse events (TRAEs), and TRAEs led to discontinuation of the study medication in 8.9% of these patients. In the PBO plus GemCis arm, 63.5% of patients experienced grade 3/4 TRAEs, and TRAEs led to discontinuation of the study medication in 11.4% of these patients. Adverse events in this follow-up were similar between treatment arms and consistent with the safety analysis previously reported.

Because of the clinically meaningful benefit and manageable safety profile of D plus GemCis versus PBO plus GemCis, it may be considered a new first-line standard of care for patients with advanced BTC.


  1. Oh DY, He AR, Qin S, et al. A phase 3, randomized, double blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients with advanced biliary tract cancer (BTC). TOPAZ-1. J Clin Oncol. 2022;40(suppl 4):378-378.

Source: Oh D, He AR, Qin S, et al. 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). Ann Oncol. 2022;33(suppl 7):S19-S26.

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