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World J Gastrointest Oncol. Jun 15, 2023; 15(6): 959-972
Published online Jun 15, 2023. doi: 10.4251/wjgo.v15.i6.959
Paradigm shift of chemotherapy and systemic treatment for biliary tract cancer
Wattana Leowattana, Tawithep Leowattana, Pathomthep Leowattana
Wattana Leowattana, Pathomthep Leowattana, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Rachatawee 10400, Bangkok, Thailand
Tawithep Leowattana, Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Wattana 10110, Bangkok, Thailand
Author contributions: Leowattana W wrote the paper; Leowattana T and Leowattana P collected the data.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wattana Leowattana, BMed, MD, MSc, PhD, Full Professor, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajavithi Road, Rachatawee 10400, Bangkok, Thailand. wattana.leo@mahidol.ac.th
Received: January 26, 2023
Peer-review started: January 26, 2023
First decision: April 11, 2023
Revised: April 14, 2023
Accepted: May 5, 2023
Article in press: May 5, 2023
Published online: June 15, 2023
Processing time: 139 Days and 17.7 Hours
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.