Pembrolizumab plus gemcitabine and cisplatin for advanced biliary tract cancer: longer-term follow-up from the randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-966 trial
In brief
Adding pembrolizumab raises 3-year survival from 11% to 13% in biliary cancer
In this randomized trial of 1,069 people with previously untreated advanced biliary tract cancer, adding pembrolizumab to gemcitabine and cisplatin sustained a survival benefit after a median 3 years of follow-up. The estimated 3-year survival difference was 2 percentage points, while severe treatment-related side effects were similarly common in both groups; the absolute benefit remains modest.
- Journal
- EClinicalMedicine (Q1)
- Published
- 12 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Makoto Ueno, Changhoon Yoo, Zhenggang Ren, Junji Furuse, Robin Kate Kelley, Stephen Lam Chan, et al.
- PMID
- 42898854
- DOI
- 10.1016/j.eclinm.2026.104213
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 21 October 2026): Pembrolizumab plus chemo improves OS in biliary tract cancer
Abstract
BACKGROUND: At the final analysis of KEYNOTE-966 (median follow-up 25·6 months), pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group) versus placebo plus gemcitabine and cisplatin (placebo group) provided a statistically significant, clinically meaningful improvement in overall survival without any new safety signals in participants with advanced biliary tract cancer. We report results from a median study follow-up of 36·6 months (∼3 years). METHODS: In the randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-966 trial conducted at 175 medical centres worldwide, eligible participants aged ≥18 years with previously untreated advanced biliary tract cancer were randomly assigned (1:1) to pembrolizumab 200 mg or placebo intravenously every 3 weeks plus gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 intravenously on days 1 and 8 of every 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease status, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population (all participants randomly assigned to a treatment). Safety was evaluated in the as-treated population, comprising all participants who received at least one dose of study treatment. As the primary endpoint was met at the final analysis, updated data are reported without p values. This study is registered at ClinicalTrials.gov, NCT04003636. FINDINGS: Between Oct 4, 2019, and June 8, 2021, 1069 participants were randomly assigned to the pembrolizumab group (n = 533) or the placebo group (n = 536). Median follow-up at data cutoff (Nov 14, 2023) was 36·6 months (IQR 32·7-41·4). The hazard ratio for overall survival was 0·86 (95% CI, 0·75-0·98) with pembrolizumab versus placebo; estimated 36-month overall survival rates were 13% (95% CI, 11-17) in the pembrolizumab group and 11% (95% CI, 8-14) in the placebo group. Grade 3 or 4 treatment-related adverse events occurred in 370 (70%) of 529 participants in the pembrolizumab group and 367 (69%) of 534 participants in the placebo group. No new treatment-related deaths occurred since the final analysis. INTERPRETATION: With extended follow-up, the survival benefit of pembrolizumab plus gemcitabine and cisplatin observed at the final analysis persists with approximately 3 years of follow-up, with no new safety signals among participants with previously untreated metastatic or unresectable biliary tract cancer. FUNDING: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.