Systemic therapy in biliary tract cancer: Up to date

Abstract

Systemic therapy for biliary tract cancer is often administered as perioperative adjuvant therapy, or as palliative therapy in cases with unresectable disease. Capecitabine is widely used overseas as postoperative adjuvant therapy, but this drug is still not approved for this use in Japan. Combined gemcitabine plus cisplatin, gemcitabine plus S-1, and gemcitabine plus cisplatin plus S-1 have been established as standard first-line treatments. Modified FOLFOX was demonstrated to yield survival benefit as second-line treatment in a UK phase III trial, and it was often used in patients who showed disease progression after gemcitabine plus cisplatin therapy. However, this treatment is not covered by insurance in Japan. In recent years, the development of molecular-targeted agents based on genomic alterations in the tumors has been progressing, and favorable treatment efficacies have been reported with IDH1 inhibitors, FGFR inhibitors, BRAF inhibitors plus MEK inhibitors, HER2 inhibitors, etc. Furthermore, development of a promising immune checkpoint inhibitor is also in progress. Pembrolizumab for microsatellite instability high tumors and ROS1/TRK inhibitors against tumors with NTRK1/2/3 fusion can be administered across cancers in various organs. Thus, it appears that rapid progress is being made in the development of systemic therapies for biliary tract cancer.