FDA Approves Pembrolizumab in Combination with Chemotherapy for Biliary Tract Cancer

The Food and Drug Administration (FDA) has granted approval for the use of pembrolizumab in conjunction with gemcitabine and cisplatin for locally advanced unresectable or metastatic biliary tract cancer (BTC). This decision, announced on October 31, 2023, stems from the positive results of the KEYNOTE-966 trial.

The multicenter, randomized, double-blind, placebo-controlled KEYNOTE-966 trial involved 1069 patients with locally advanced unresectable or metastatic BTC who had not undergone prior systemic therapy for advanced disease. Participants were randomly assigned in a 1:1 ratio to either receive pembrolizumab alongside gemcitabine and cisplatin every 3 weeks or a placebo with the same chemotherapy schedule. The treatment continued until unacceptable toxicity or disease progression, with a maximum of 8 cycles of cisplatin. Gemcitabine was continued at the discretion of the physician, and pembrolizumab or placebo were continued until disease progression, unacceptable toxicity, or a maximum of 2 years.

The primary measure of efficacy was overall survival (OS). The combination of pembrolizumab and chemotherapy demonstrated a statistically significant improvement in OS compared to the placebo plus chemotherapy, with a hazard ratio of 0.83 (95% CI: 0.72, 0.95; one-sided p-value = 0.0034). The median OS was 12.7 months (95% CI: 11.5, 13.6) for the pembrolizumab group, compared to 10.9 months (95% CI: 9.9, 11.6) for the placebo group.

Adverse reactions leading to the interruption of pembrolizumab occurred in 55% of patients. The most common adverse reactions or laboratory abnormalities (≥2%) leading to interruption included decreased neutrophil count, decreased platelet count, anemia, decreased white blood cell count, pyrexia, fatigue, cholangitis, increased ALT, increased AST, and biliary obstruction.

The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression or unacceptable toxicity. Administration should occur before chemotherapy when given on the same day.

This approval was granted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, facilitating concurrent submission and review of oncology drugs among international partners. Regulatory agencies in other countries are currently reviewing the applications as part of this initiative. 

The FDA used the Assessment Aid, a voluntary submission from the applicant to streamline the assessment process. The success of this expedited review underscores the collaborative efforts between regulatory bodies and the pharmaceutical industry to bring innovative and effective treatments to patients more swiftly.

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