Update for: New developments in systemic therapy for advanced biliary tract cancer.

Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the gallbladder, ampullary carcinoma, and intrahepatic cholangiocarcinoma are often identified at advanced stages. The standard therapy for advanced biliary tract cancer has been a combination of cytotoxic agents. Globally, gemcitabine plus cisplatin has been the standard first-line regimen, whereas gemcitabine plus cisplatin plus S-1 and gemcitabine plus S-1 have also been the standard regimens in Japan. Recently, treatment strategies have been updated. As first-line systemic therapy, the addition of an immune checkpoint inhibitor, such as durvalumab or pembrolizumab, to gemcitabine plus cisplatin has been shown to prolong overall survival compared with gemcitabine plus cisplatin. These combined immunotherapies are widely used in clinical practice as internationally standard first-line regimens. Regarding second-line treatment after a gemcitabine-based regimen, fluorouracil and folinic acid plus oxaliplatin have been the standard regimen. Additionally, FGFR2 fusion gene/rearrangement, mutations of IDH1/2, KRAS, and BRAF, and overexpression of HER2 are promising therapeutic targets for which the effectiveness of each targeted therapy has been reported, at this time, as a second-line or later treatment.