FDA approves pembrolizumab with chemotherapy for biliary tract cancer

FDA approval (Oct 31, 2023)

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

Evidence base: KEYNOTE-966 (NCT04003636)

Approval was supported by KEYNOTE-966, a multicenter, randomized, double-blind, placebo-controlled trial enrolling 1,069 patients with locally advanced unresectable or metastatic BTC who had not received prior systemic therapy for advanced disease.

Patients were randomized 1:1 to:

• Pembrolizumab Day 1 + gemcitabine/cisplatin Days 1 and 8 every 3 weeks, or
• Placebo Day 1 + gemcitabine/cisplatin on the same schedule.

Treatment continued until unacceptable toxicity or disease progression. Cisplatin was given for a maximum of 8 cycles; gemcitabine could continue at physician discretion. Pembrolizumab/placebo could continue up to 2 years.

Efficacy

Primary efficacy measure was overall survival (OS).

• OS improved with pembrolizumab + chemotherapy vs placebo + chemotherapy: HR 0.83 (95% CI, 0.72–0.95; one-sided p=0.0034)
• Median OS: 12.7 months (95% CI, 11.5–13.6) vs 10.9 months (95% CI, 9.9–11.6)

Safety and dosing (selected)

Adverse reactions leading to pembrolizumab interruption occurred in 55%. Common causes (≥2%) included cytopenias, pyrexia, fatigue, cholangitis, elevated ALT/AST, and biliary obstruction.

Recommended pembrolizumab dose: 200 mg q3w or 400 mg q6w until disease progression or unacceptable toxicity; administer prior to chemotherapy when given the same day.

Regulatory context

The review was conducted under Project Orbis; reviews at other agencies were noted as ongoing.