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. 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 were presented at the 2022 ASCO GI Cancers Symposium and 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 it was 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 disease, respectively. For primary tumor location, the OS HR for intrahepatic cholangiocarcinoma (CCA) was 0.78 (95% CI, 0.62-0.99), the OS HR for extrahepatic CCA 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.
Sources: 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.
Oh DY, He, AR, Qin S. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. American Society of Clinical Oncology Gastrointestinal Cancers Symposium 2022. Abstract 378.
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