Pembrolizumab Wins Biliary Tract Cancer Indication

The US Food and Drug Administration approved pembrolizumab (Keytruda, Merck) for locally advanced unresectable or metastatic biliary tract cancer in combination with gemcitabine and cisplatin.

With the new approval, the anti-PD-1 checkpoint inhibitor is now indicated across 20 tumor types, including six gastrointestinal cancer indications. 

Approval for unresectable/metastatic biliary tract cancer was based on the KEYNOTE-966 trial which randomized 1069 patients equally to either pembrolizumab 200 mg or placebo on day 1 one of 3 weeks cycles with gemcitabine and cisplatin delivered on days 1 and 8. Cisplatin was administered for a maximum of eight cycles; gemcitabine was continued at physician’s discretion, and pembrolizumab/placebo continued until disease progression or unacceptable toxicity for a maximum of 2 years.

Median overall survival was 12.7 months in the pembrolizumab arm vs 10.9 months with placebo (hazard ratio, 0.83; P=.0034). Median progression free survival was 6.5 months with pembrolizumab vs 5.6 months, but the difference was not statistically significant.

The median duration of exposure to pembrolizumab was 6 months with 15% of patients discontinuing due to adverse events.

Adverse events leading to pembrolizumab interruption occurred in 55% of patients. The most common were decreased neutrophil count, decreased platelet count, anemia, decreased white blood cell count, pyrexia, fatigue, cholangitis, increased ALT, increased AST, and biliary obstruction.

In a press release announcing the approval, Merck noted that pyrexia was more common in the pembrolizumab arm (26% vs 20%) as well as rash (21% vs 13%), pruritus (15% vs 10%), and hypothyroidism (9% vs 2.6%). There were no clinically meaningful differences in the incidence of grade 3/4 toxicities between the arms.

Merck also noted that immune-mediated adverse events can occur at any time during or after treatment with pembrolizumab, which include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications from allogeneic hematopoietic stem cell transplantation. 

The recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression or unacceptable toxicity. FDA noted that pembrolizumab should be administered prior to chemotherapy when given on the same day.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]

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