On September 2, 2022, the FDA accelerated the approval of durvalumab (Imfinzi; AstraZeneca), a PD-L1 inhibitor, in combination with gemcitabine and cisplatin, for adults with locally advanced or metastatic biliary tract cancer.
Durvalumab was previously approved for unresectable, stage III non–small-cell lung cancer and for first-line treatment of extensive-stage small-cell lung cancer.
The approval of the new indication was based on results of the randomized, double-blind, placebo-controlled, multiregional TOPAZ-1 clinical trial of 685 patients with histologically confirmed, locally advanced, unresectable or metastatic biliary tract cancer (including 56% of patients with intrahepatic cholangiocarcinoma, 25% of patients with gallbladder cancer, and 19% with extrahepatic cholangiocarcinoma).
The patients were randomized 1:1 to durvalumab plus chemotherapy or to placebo plus chemotherapy and continued treatment until disease progression or unacceptable adverse events.
The median overall survival was 12.8 months in the durvalumab plus chemotherapy arm and 11.5 months in the placebo plus chemotherapy arm (95% confidence interval, 10.1-12.5). The median progression-free survival was 7.2 months with durvalumab and 5.7 months with placebo. The investigator-assessed overall response rate was 27% with durvalumab and 19% with placebo.
The most common (≥20%) adverse events were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.