Integrating cytotoxic, targeted and immune therapies for cholangiocarcinoma

Abstract

Management of BTCs is rapidly evolving. Majority of patients are diagnosed with advanced disease, when chemotherapy with cisplatin and gemcitabine followed by second-line FOLFOX is the cornerstone of treatment in the absence of targetable alterations. Targeted therapies for tumours harbouring fibroblast growth factor receptor-2 (FGFR-2) fusions, isocitrate dehydrogenase-1 (IDH-1) mutations, BRAF V600E mutations, NTRK fusions and/or HER2 amplifications, among others, have brought precision medicine into the treatment landscape of advanced BTC. This holds true especially for patients with intrahepatic cholangiocarcinoma. Recently, immunotherapy has also shown promising activity. The field is now moving forward and management is no longer limited to chemotherapy or targeted therapies alone, but really looking into how combination strategies could enhance response to treatment. We are therefore facing a change of paradigm, where immunotherapy, cytotoxic chemotherapy and targeted therapies will complement each other when administered concomitantly. This review will focus on the rational behind these combinations and summarise current clinical trial data.