Patients with advanced biliary tract cancer have poor prognosis, and first-line standard of care, gemcitabine plus cisplatin, has remained unchanged for over 10 years. TOPAZ-1 evaluated durvalumab plus chemotherapy in patients with advanced biliary tract cancer.
In this double-blind, placebo-controlled, phase 3 study, patients with previously untreated unresectable or metastatic biliary tract cancer, or recurrent disease, were randomized 1:1 to receive durvalumab or placebo in combination with gemcitabine plus cisplatin for up to 8 cycles, followed by durvalumab or placebo monotherapy until disease progression or unacceptable toxicity. The primary objective was to assess overall survival. Secondary endpoints included progression-free survival, objective response rate, and safety.
Overall, 685 patients were randomized to durvalumab (n=341) or placebo (n=344) with chemotherapy. As of data cutoff, 198 (58.1%) patients in the durvalumab group and 226 (65.7%) patients in the placebo group had died. The hazard ratio for overall survival was 0.80 (95% confidence interval [CI], 0.66–0.97; P=0.021). The estimated 24-month overall survival rate (95% CI) was 24.9% (17.9–32.5) for durvalumab and 10.4% (4.7–18.8) for placebo. The hazard ratio for progression-free survival was 0.75 (95% CI, 0.63–0.89; P=0.001). Objective response rates were 26.7% with durvalumab and 18.7% with placebo. The incidences of grade 3 or 4 treatment-related adverse events were 62.7% and 64.9% with durvalumab and placebo, respectively.
Durvalumab plus chemotherapy significantly improved OS versus placebo plus chemotherapy, and the safety profiles of the two treatment groups were similar (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03875235.)