Pembrolizumab Plus Chemotherapy Approved for Treatment of Patients With Biliary Tract Cancer

The US Food and Drug Administration (FDA) has granted approval to pembrolizumab with gemcitabine and cisplatin for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer.

This regulatory decision was based on efficacy results from the multicenter, double-blind, placebo-controlled phase 3 KEYNOTE-966 trial.

The KEYNOTE-966 trial enrolled 1069 patients with locally advanced unresectable or metastatic biliary tract cancer who had not received prior systemic therapy for advanced disease. Patients were randomized on a 1-to-1 basis to receive either pembrolizumab plus gemcitabine and cisplatin, or placebo plus gemcitabine and cisplatin. Pembrolizumab or placebo was administered on Day 1, with chemotherapy administered on Day 1 and Day 8, every 3 weeks. Cisplatin was continued for a maximum of 8 cycles, while gemcitabine was continued at the physician’s discretion. Pembrolizumab or placebo was continued until disease progression, unacceptable toxicity, or a maximum of 2 years. The main efficacy outcome was overall survival (OS).

The median OS in the pembrolizumab arm was 12.7 months, compared with 10.6 months in the placebo arm. This demonstrated a statistically significant improvement with pembrolizumab plus chemotherapy compared with placebo plus chemotherapy (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.72 to 0.95; one-sided P = .0034). The most common adverse reactions or laboratory abnormalities, occurring in ≥2% of patients, which led to a dose interruption, were decreased neutrophil count, decreased platelet count, anemia, decreased white blood cell count, pyrexia, fatigue, cholangitis, increased alanine transaminase (ATL), increased aspartate aminotransferase (AST), and biliary obstruction.

The FDA-recommended dose for pembrolizumab is 200 mg every 3 weeks, or 400 mg every 6 weeks. When pembrolizumab is administered on the same day as gemcitabine and cisplatin, it should be administered prior to the chemotherapy.

Source:

US Food and Drug Administration. FDA approves pembrolizumab with chemotherapy for biliary tract cancer. November 1, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-biliary-tract-cancer