Immunotherapy for Biliary Tract Cancers 

The FDA has approved the immune checkpoint inhibitor pembrolizumab for certain advanced cancers of the biliary tract. 

The U.S. Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda), in combination with gemcitabine (Gemzar) and cisplatin, for the treatment of locally advanced unresectable or metastatic biliary tract cancer. 

Pembrolizumab is a type of immunotherapy called an immune checkpoint inhibitor. It blocks one of the cell’s immune checkpoints, a signaling pathway that keeps the immune system from reacting too strongly. Because cancer cells often exploit these pathways to hide from the immune system, immune checkpoint inhibitors can help the immune system recognize and destroy cancer cells. 

An illustrated X-ray of a human's chest and torso with the gallbladder highlighted, which is where biliary tract cancer, or cholangiocarcinoma, is found.

Pembrolizumab blocks the immune checkpoint protein PD-1, expressed on immune cells. It was previously approved for use in several cancer types, including all advanced solid tumors that have a high tumor mutation burden (a large number of mutations per segment of DNA) or microsatellite instability (a marker of unstable DNA). The current approval allows some patients with biliary tract cancers that do not display these genomic characteristics to receive pembrolizumab. 

The approval was based on results from KEYNOTE-966, a phase III, multicenter, randomized, double-blind, placebo-controlled trial that enrolled 1,069 patients with locally advanced unresectable or metastatic biliary tract cancer who had not previously received systemic therapy in the advanced disease setting. Patients received gemcitabine and cisplatin and were randomly assigned 1:1 to receive pembrolizumab or placebo. Treatment with pembrolizumab or placebo continued for a maximum of two years or until disease progression or unacceptable toxicity. 

The median overall survival was 12.7 months for patients in the pembrolizumab arm and 10.9 months for patients in the placebo arm, a statistically significant difference. 

Biliary tract cancer, also called cholangiocarcinoma, is a rare but aggressive tumor type that arises in the gallbladder or in the tubes and ducts that carry bile through and around the liver. An estimated 8,000 people are diagnosed with biliary tract cancer in the United States each year. 

The FDA rendered its decision on October 31, 2023.