Pembrolizumab Approved for Biliary Tract Cancer

Cholangiocarcinoma CT scan.

The FDA has approved pembrolizumab (Keytruda®, Merck) in combination with gemcitabine and cisplatin for locally advanced unresectable or metastatic biliary tract cancer (BTC).  

Why it matters: “Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide,” wrote Robin Kate Kelley, MD, a Gastrointestinal Oncologist at The University of California, San Francisco, and colleagues, in their published results of the KEYNOTE-966 trial (NCT04003636), on which approval was based. “We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer.”

What they studied: Safety and efficacy were studied in the phase 3, multicenter, double-blind, placebo-controlled trial in which 1,069 patients with locally advanced unresectable or metastatic BTC were randomized 1:1 to receive either 200 mg of pembrolizumab on Day 1 plus gemcitabine and cisplatin on Day 1 and Day 8 every three weeks, or placebo on Day 1 plus gemcitabine and cisplatin on Day 1 and Day 8 every three weeks. Treatment was continued until disease progression, unacceptable toxicity, or for a maximum of two years. Cisplatin was administered for a maximum of eight cycles, and gemcitabine was continued per the physician’s discretion.

The primary end point measured was overall survival.

What they found: At a median follow-up at final analysis of 25.6 months, pembrolizumab plus chemotherapy saw a statistically significant improvement with a median overall survival of 12.7 months compared with placebo plus chemotherapy at a median of 10.9 months.

Adverse events: The most common adverse events or laboratory abnormalities that lead to treatment interruption in ≥2% of patients were decreased neutrophil count, decreased platelet count, anemia, decreased white blood cell count, pyrexia, fatigue, cholangitis, increased alanine transaminase (ALT), increased aspartate aminotransferase (AST), and biliary obstruction. Adverse events leading to the interruption of pembrolizumab occurred in 55% of patients.

Conclusion: “Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer,” concluded Dr. Kelley and colleagues.

Instructions: The recommended dosage of pembrolizumab is 200 mg every three weeks or 400 mg every six weeks until disease progression or unacceptable toxicity. Pembrolizumab should be administered prior to chemotherapy when given on the same day.

For More Information

Kelley RK, Ueno M, Yoo C, et al (2023). Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 401(10391):1853-1865. DOI:10.1016/S0140-6736(23)00727-4 (2023). Pembrolizumab (MK-3475) plus gemcitabine/cisplatin versus placebo plus gemcitabine/cisplatin for first-line advanced and/or unresectable biliary tract carcinoma (BTC) (MK-3475-966/KEYNOTE-966) (KEYNOTE-966). NLM identifier: NCT04003636.

Keytruda® (pembrolizumab) prescribing information (2023). Merck. Available at:

US Food and Drug Administration (2023). FDA approves pembrolizumab with chemotherapy for biliary tract cancer. Available at:

Image credit: Samir. Licensed under CC BY-SA 3.0 DEED

Related Articles


Your email address will not be published. Required fields are marked *