Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response

Cancer Res Treat. 2020 Apr;52(2):594-603. doi: 10.4143/crt.2019.493. Epub 2019 Dec 18.


Purpose: The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated.

Materials and methods: In this prospective cohort study, programmed death ligand-1 (PD-L1)-positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks.

Results: Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049).

Conclusion: Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1-positive BTC patients. In patients who showed objective response, durable response could be achieved.

Keywords: Biliary tract cancer; Cholangiocarcinoma; Immunotherapy; Pembrolizumab.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Bile Duct Neoplasms / drug therapy*
  • Biomarkers / blood*
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Prospective Studies


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Biomarkers
  • pembrolizumab