Paradigm shift of chemotherapy and systemic treatment for biliary tract cancer

Abstract

Biliary tract cancers (BTC) are frequently identified at late stages and have a poor prognosis due to limited systemic treatment regimens. For more than a decade, the combination of gemcitabine and cis-platin has served as the first-line standard treatment. There are few choices for second-line chemo-therapy. Targeted treatment with fibroblast growth factor receptor 2 inhibitors, neurotrophic tyrosine receptor kinase inhibitors, and isocitrate dehydrogenase 1 inhibitors has had important results. Immune checkpoint inhibitors (ICI) such as pembrolizumab are only used in first-line treatment for microsatellite instability high patients. The TOPAZ-1 trial's outcome is encouraging, and there are several trials underway that might soon put targeted treatment and ICI combos into first-line options. Newer targets and agents for existing goals are being studied, which may represent a paradigm shift in BTC management. Due to a scarcity of targetable mutations and the higher toxicity profile of the current medications, the new category of drugs may occupy a significant role in BTC therapies.

Keywords: Biliary tract cancers, Gemcitabine and cisplatin combination, Fibroblast growth factor receptor 2 inhibitors, Isocitrate dehydrogenase 1 inhibitors, Neurotrophic tyrosine receptor kinase gene fusion inhibitors, Immune checkpoint inhibitors, Microsatellite instability high, Infrigatinib, Pemigatinib

Core Tip: There have been several developments in the field of advanced biliary tract cancer (BTC) therapy in recent years. First, the care of these hepatobiliary malignancies has improved as a result of better knowledge of the molecular basis of BTC. The Food and Drug Administration's approval of pemigatinib, infigratinib, and ivosidenib for fibroblast growth factor receptor 2-rearranged and isocitrate dehydrogenase 1-mutant cholangiocarcinoma illustrates the paradigm shift that the arrival of targeted agents has really brought about. Second, patients receiving modified fluorouracil, oxaliplatin, and liposomal irinotecan with fluorouracil-leucovorin, respectively, as second-line treatments after progressing to first-line cisplatin-gemcitabine, showed an overall survival advantage in the newly released Advanced Biliary Tract Cancer-06 and NIFTY studies.