Addition of Durvalumab to First-Line Chemotherapy in Advanced Biliary Cancer

Standard chemotherapy for metastatic biliary cancer consists of the combination of gemcitabine and cisplatin. Genomic profiling of these cancers is mandatory, given recent approval of molecularly targeted therapies.

Investigators report results of the international, industry-sponsored, phase 3 TOPAZ-1 trial, in which 685 patients with advanced biliary cancer were randomized to treatment with gemcitabine and cisplatin for up to eight 21-day cycles combined with either placebo or the anti–PD-L1 agent durvalumab, followed by maintenance therapy with placebo or durvalumab.

Patients had a median age of 64, most were treated in Asia (55%), and most had intrahepatic primary tumors (56%), followed by gallbladder (25%) and extrahepatic (19%) primary tumors. Most patients had PD-L1 tumor-area positivity (TAP) scores ≥1% (59%).

At a median follow-up of approximately 16 months, the primary endpoint of overall survival was improved in the durvalumab arm compared with the placebo arm (median, 12.8 vs. 11.5 months; hazard ratio, 0.80; P=0.021). Estimated overall survival rates were improved with durvalumab at 12 months (54.1% vs. 48.0%), 18 months (35.1% vs. 25.6%), and 24 months (24.9% vs. 10.4%). Progression-free survival (median, 7.2 vs. 5.7 months; HR, 0.75; P=0.001) and response rate (26.7% vs. 18.7%) also were improved with durvalumab. Incidence of grade 3/4 immune-related adverse events was 2.4% with durvalumab and 1.5% with placebo. Overall survival benefits were similar for TAP-positive (HR, 0.79) and TAP-negative (HR, 0.86) patients.