Systemic therapies for intrahepatic cholangiocarcinoma

J Hepatol. 2020 Feb;72(2):353-363. doi: 10.1016/j.jhep.2019.10.009.


Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary neoplasm whose incidence is increasing. Largely neglected for decades as a rare malignancy and frequently misdiagnosed as carcinoma of unknown primary, considerable clinical and investigative attention has recently been focused on iCCA worldwide. The established standard of care includes first-line (gemcitabine and cisplatin), second-line (FOLFOX) and adjuvant (capecitabine) systemic chemotherapy. Compared to hepatocellular carcinoma, iCCA is genetically distinct with several targetable genetic aberrations identified to date. Indeed, FGFR2 and NTRK fusions, and IDH1 and BRAF targetable mutations have been comprehensively characterised and clinical data is emerging on targeting these oncogenic drivers pharmacologically. Also, the role of immunotherapy has been examined and is an area of intense investigation. Herein, in a timely and topical manner, we will review these advances and highlight future directions of research.

Keywords: Adjuvant therapy; Checkpoint inhibitors; FGFR; IDH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / epidemiology
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / immunology
  • Chemotherapy, Adjuvant / methods*
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / epidemiology
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / immunology
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunotherapy / methods*
  • Incidence
  • Molecular Targeted Therapy / methods*
  • Treatment Outcome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology


  • Antineoplastic Agents
  • Immune Checkpoint Inhibitors