On September 2, 2022, the FDA accelerated the approval of durvalumab (Imfinzi; AstraZeneca), a PD-L1–blocking antibody, in combination with gemcitabine and cisplatin, for the treatment of locally advanced or metastatic biliary tract cancer in adults.
Durvalumab was previously approved for the treatment of unresectable, stage III non–small-cell lung cancer after concurrent platinum-based chemotherapy and radiation, and, in combination with etoposide and carboplatin or cisplatin, for the first-line treatment of extensive-stage small-cell lung cancer.
The approval of this new indication was based on the results of the randomized, double-blind, placebo-controlled, multiregional TOPAZ-1 trial that enrolled patients with histologically confirmed, locally advanced, unresectable or metastatic biliary tract cancer who had not previously received systemic treatment for metastatic disease.
The study included 685 patients, and there was a significant improvement in overall survival (OS) in those who received durvalumab plus gemcitabine and cisplatin versus those who received placebo plus gemcitabine and cisplatin. The median OS was 12.8 months in the durvalumab arm and 11.5 months in the placebo arm (95% confidence interval [CI], 10.1-12.5). The median progression-free survival was 7.2 months with durvalumab (95% CI, 6.7-7.4) versus 5.7 months with placebo (95% CI, 5.6-6.7). The investigator-assessed overall response rates were 27% (95% CI, 22%-32%) with durvalumab and 19% (95% CI, 15%-23%) with placebo.
The most common (≥20%) adverse events were fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.
In combination with gemcitabine and cisplatin, the recommended dose of durvalumab is 1500 mg every 3 weeks in patients who weigh ≥30 kg, followed by 1500 mg every 4 weeks as monotherapy until disease progression or unacceptable toxicity. For patients who weigh <30 kg, durvalumab should be dosed at 20 mg/kg every 3 weeks in combination with gemcitabine and cisplatin, followed by a dose of 20 mg/kg every 4 weeks until disease progression or unacceptable adverse events.
