Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the 
gall bladder, ampullary carcinoma and intrahepatic cholangiocarcinoma are often 
identified at an advanced stage and have poor prognoses. Although effective 
chemotherapy regimens are needed, their development remains unsatisfactory. From 
the results of a phase III clinical trial (ABC-02 trial), gemcitabine plus 
cisplatin is the standard first-line chemotherapeutic regimen for advanced 
biliary tract cancer. A phase III trial of gemcitabine plus cisplatin vs. 
gemcitabine plus S-1 therapy (FUGA-BT) demonstrated the non-inferiority of 
gemcitabine plus S-1 to gemcitabine plus cisplatin. A phase III trial of 
gemcitabine plus cisplatin vs. gemcitabine plus cisplatin plus S-1 (MITSUBA) was 
conducted, and the report on the results of the final analysis is being awaited. 
A standard second-line chemotherapeutic regimen has not yet been established. 
Fluoropyrimidines are frequently used in clinical practice. Despite many 
clinical trials being conducted with molecular targeted agents including 
erlotinib, cetuximab, panitumumab, bevacizumab, sorafenib, cediranib, trametinib 
and vandetanib, no agent has shown to be effective for advanced biliary tract 
cancer. Next-generation sequencing shows great promise by allowing rapid 
mutational analysis of multiple genes in human cancers, and attractive driver 
genetic alterations have been reported in biliary tract cancer. FGFR2 fusion 
gene, mutations of IDH1/2, BRAF, BRCA1/2, ATM, PIK3CA and overexpression of 
c-MET and HER2/neu are reported relatively frequently and are interesting 
targets. Therefore, future development in precision medicine utilizing 
next-generation sequencing is expected. Although the efficacy of immune 
checkpoint inhibitors, such as anti-PD-1, anti-PD-L1 and anti-CTLA4 antibodies, 
remains unknown at present, basic data and results of ongoing clinical trials 
are anticipated.