Third-Line Palliative Systemic Therapy for Advanced Biliary Tract Cancer: Multicentre Review of Patterns of Care and Outcomes

Simon Gray, Octave Letissier, Constance D’abrigeon, Dinakshi Shah, Stephen Wardell, Olusola Faluyi, Angela Lamarca, Richard A. Hubner, Julien Edeline, Juan W. Valle, Mairéad G. Mcnamara

Research output: Contribution to journalArticlepeer-review


Phase 3 trials have established standard first-line (1L) and 2L systemic therapy options for patients with advanced biliary cancer (ABC). However, a standard 3L treatment remains undefined. Clinical practice and outcomes for 3L systemic therapy in patients with ABC were therefore evaluated from three academic centres. Included patients were identified using institutional registries; demographics, staging, treatment history, and clinical outcomes were collected. Kaplan-Meier methods were used to assess progression-free survival (PFS) and overall survival (OS). Ninety-seven patients, treated between 2006 and 2022, were included; 61.9% had intrahepatic cholangiocarcinoma. At the time of analysis, there had been 91 deaths. Median PFS from initiating 3L palliative systemic therapy (mPFS3) was 3.1 months (95%CI 2.0-4.1), while mOS3 was 6.4 months (95%CI 5.5-7.3); mOS1 was 26.9 months (95%CI 23.6-30.2). Among patients with a therapy-targeted molecular aberration (10.3%; n = 10; all received in 3L), mOS3 was significantly improved versus all other included patients (12.5 vs. 5.9 months; p = 0.02). No differences in OS1 were demonstrated between anatomical subtypes. Fourth-line systemic therapy was received by 19.6% of patients (n = 19). This international multicentre analysis documents systemic therapy use in this select patient group, and provides a benchmark of outcomes for future trial design.

Original languageEnglish
Article number3047
Issue number11
Publication statusPublished - 3 Jun 2023


  • biliary tract
  • cholangiocarcinoma
  • gallbladder
  • ampulla of Vater
  • third-line
  • systemic therapy
  • chemotherapy
  • targeted therapy


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