The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On October 31, 2023, the Food and Drug Administration approved pembrolizumab (Keytruda, Merck) to be used with gemcitabine and cisplatin for locally advanced unresectable or metastatic biliary tract cancer (BTC).
Efficacy was evaluated in KEYNOTE-966 (NCT04003636), a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 1069 patients with locally advanced unresectable or metastatic BTC who had not received prior systemic therapy for advanced disease. Patients were randomized (1:1) to receive either pembrolizumab on Day 1 plus gemcitabine and cisplatin on Day 1 and Day 8 every 3 weeks, or placebo on Day 1 plus gemcitabine and cisplatin on the above schedule. Treatment continued until unacceptable toxicity or disease progression. Cisplatin was administered for a maximum of 8 cycles; gemcitabine was continued at the physician’s discretion. Pembrolizumab or placebo were continued until disease progression, unacceptable toxicity, or a maximum of 2 years.
The major efficacy measure was overall survival (OS). Pembrolizumab plus chemotherapy demonstrated a statistically significant improvement in OS compared to placebo plus chemotherapy with a hazard ratio of 0.83 (95% Confidence Interval [CI]: 0.72, 0.95); one-sided p-value=0.0034). The median OS was 12.7 months (95% CI: 11.5, 13.6) and 10.9 months (95% CI: 9.9, 11.6) in the respective arms.
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 were decreased neutrophil count, decreased platelet count, anemia, decreased white blood cell count, pyrexia, fatigue, cholangitis, increased ALT, increased AST, and biliary obstruction.
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression or unacceptable toxicity. Pembrolizumab should be administered prior to chemotherapy when given on the same day.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 4 months ahead of the FDA goal date.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.