On October 31, 2023, pembrolizumab (Keytruda) was approved for use with ­gemcitabine/cisplatin in first-line treatment of patients with locally advanced unresectable or metastatic biliary tract cancer.¹

Supporting Efficacy Data

Approval was based on the double-blind KEYNOTE-966 trial (ClinicalTrials.gov identifier NCT04003636). In this study, patients were randomly assigned to receive pembrolizumab at 200 mg (n = 533) or placebo (n = 539) on day 1 with gemcitabine at 1,000 mg/m² and cisplatin at 25 mg/m² on days 1 and 8 every 3 weeks. Cisplatin was administered for a maximum of eight cycles; gemcitabine was continued at the physician’s discretion. Pembrolizumab and placebo were continued until disease progression, unacceptable toxicity, or a maximum of 2 years.

Median overall survival, the primary endpoint, was 12.7 months (95% confidence interval [CI] = 11.5–13.6 months) in the pembrolizumab group vs 10.9 months (95% CI = 9.9–11.6 months) in the control group (hazard ratio = 0.83, 95% CI = 0.72–0.95, P = .0034). Median progression-free survival was 6.5 months (95% CI = 5.7–6.9 months) in the pembrolizumab group vs 5.6 months (95% CI = 5.1–6.6 months) in the control group (HR = 0.86, 95% CI = 0.75–1.00, P was not significant).

How It Is Used

The recommended dose of pembrolizumab 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.

Safety Profile

In KEYNOTE-966, adverse events of any grade with an incidence ≥ 5% in the pembrolizumab group vs the control group were pyrexia (26% vs 20%), rash (21% vs 13%), pruritus (15% vs 10%), and hypothyroidism (9% vs 2.6%). No clinically meaningful difference in the incidence of grade 3 or 4 adverse events was observed between the two groups. Pembrolizumab was discontinued because of adverse events in 15% of patients, most commonly pneumonitis (1.3%).

Pembrolizumab has warnings or precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving pembrolizumab. 

REFERENCE

1. Keytruda (pembrolizumab) injection, for intravenous use, prescribing information, Merck & Co, Inc, October 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125514s144lbl.pdf. Accessed November 29, 2023.