Second line drug therapy for biliary cancer

Biliary cancer is a group of tumors that develop from the epithelium of the intra- and extrahepatic bile ducts (cholangiocarcino-ma), as well as the gallbladder. For 10 years, chemotherapy based on a combination of gemcitabine and cisplatin has remained the standard of first-line therapy in patients with locally advanced or metastatic biliary cancer, resulting in a median overall survival of 11.7 months. With the progression of the disease on the first line, effective options did not previously exist. Attempts to use various chemotherapeutic regimens, both in monotherapy and in combination, have not been successful. In order not to leave the patient without treatment, fluoropyrimidines, their combinations with oxaliplatin or irinotecan, are empirically prescribed as follow-up therapy. In recent years, different subtypes of biliary tract cancer have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma novel therapeutic targets have been identified, including fibroblast growth factor receptor gene fusions 2 (FGFR2) and isocitrate dehydrogenase 1 and 2 mutations (IDH1/2), with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both intrahepatic cholangiocarcinoma and other subtypes of biliary tract cancer, alongside targeting of the immune microenvironment. The growing knowledge of biliary tract cancer biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. In this review, we review recently published data on the use of second-line therapy after progression with standard first-line therapy in patients with biliary cancer.