Immunotherapy

An international, multicenter, phase III study (TOPAZ-1 [NCT03875235]) included 685 patients with locally advanced, recurrent, or metastatic biliary tract cancer that was unresectable and previously untreated. Patients were randomly assigned to receive either durvalumab or placebo with cisplatin plus gemcitabine for up to eight cycles, followed by durvalumab or placebo maintenance until disease progression or unacceptable toxicity occurred. The primary end point was OS. After a median follow-up of 23.4 months for patients in the durvalumab arm, the following results were observed:[12,13]

An international, multicenter, phase III study (TOPAZ-1 [NCT03875235]) included 685 patients with locally advanced, recurrent, or metastatic biliary tract cancer that was unresectable and previously untreated. Patients were randomly assigned to receive either durvalumab or placebo with cisplatin plus gemcitabine for up to eight cycles, followed by durvalumab or placebo maintenance until disease progression or unacceptable toxicity occurred. The primary end point was OS. After a median follow-up of 23.4 months for patients in the durvalumab arm, the following results were observed:[12,13]

The median OS was significantly improved in the durvalumab group (12.9 months) compared with the placebo group (11.3 months) (HR, 0.76; 95% CI, 0.64–0.91). In the durvalumab group, the 18-month OS rate was 35.1% and the 24-month OS rate was 24.9%. In the placebo group, the 18-month OS rate was 25.5% and the 24-month OS rate was 10.4%.[12,13][Level of evidence A1]

An international, multicenter, phase III study (TOPAZ-1 [NCT03875235]) included 685 patients with locally advanced, recurrent, or metastatic biliary tract cancer that was unresectable and previously untreated. Patients were randomly assigned to receive either durvalumab or placebo with cisplatin plus gemcitabine for up to eight cycles, followed by durvalumab or placebo maintenance until disease progression or unacceptable toxicity occurred. The primary end point was OS. After a median follow-up of 23.4 months for patients in the durvalumab arm, the following results were observed:[12,13]

There was no significant difference between groups in the number of grade 3 or 4 treatment-related adverse events or the number of events leading to discontinuation of a study medication.

An international, multicenter, phase III study (KEYNOTE-966 [NCT04003636]) enrolled 1,069 patients with previously untreated, unresectable, locally advanced or metastatic biliary tract cancer. Patients were randomly assigned to receive either pembrolizumab or placebo for up to 35 cycles. This was combined with gemcitabine (with no maximum duration) and cisplatin for up to 8 cycles. After a median follow-up of 25.6 months, the following results were observed:[11][Level of evidence A1]

An international, multicenter, phase III study (KEYNOTE-966 [NCT04003636]) enrolled 1,069 patients with previously untreated, unresectable, locally advanced or metastatic biliary tract cancer. Patients were randomly assigned to receive either pembrolizumab or placebo for up to 35 cycles. This was combined with gemcitabine (with no maximum duration) and cisplatin for up to 8 cycles. After a median follow-up of 25.6 months, the following results were observed:[11][Level of evidence A1]

The median OS was 12.7 months in the pembrolizumab group and 10.9 months in the placebo group (HR, 0.83; 95% CI, 0.72–0.95; one-sided P = .0034).

An international, multicenter, phase III study (KEYNOTE-966 [NCT04003636]) enrolled 1,069 patients with previously untreated, unresectable, locally advanced or metastatic biliary tract cancer. Patients were randomly assigned to receive either pembrolizumab or placebo for up to 35 cycles. This was combined with gemcitabine (with no maximum duration) and cisplatin for up to 8 cycles. After a median follow-up of 25.6 months, the following results were observed:[11][Level of evidence A1]

There was no difference in the total frequency of treatment-related adverse events between treatment groups, including grade 3 or grade 4 events. Death due to treatment-related adverse events was seen in a total of eight patients (2%) in the pembrolizumab arm and three patients (1%) in the placebo arm.