Treating biliary tract cancers

Biliary tract cancers (BTCs: gallbladder cancer, intrahepatic and extrahepatic cholangiocarcinoma) are heterogeneous malignancies with very different epidemiological, clinical and molecular characteristics. They are very aggressive tumors, often refractory to chemotherapy and associated with an overall poor prognosis. Surgical resection remains the only potentially curative treatment option, but less than 30% present with resectable disease. Recent evidence from the BILCAP trial has established capecitabine as the standard of adjuvant treatment care. Unfortunately, most patients are diagnosed at an advanced disease stage. In addition to first and second line chemotherapies (CisGem and FOLFOX, respectively), novel targeted therapy and immunotherapy strategies will play an important role in advancing therapeutic approaches to biliary tract cancers. Therapies targeting IDH-1, FGFR-2, BRAF, HER-2, NTRK genomic alterations have demonstrated clinical benefit for patients with BTC. The addition of durvalumab, a monoclonal antibody targeting the immune checkpoint programmed cell death ligand-1, to CisGem in the first-line treatment of advanced BTC has shown an overall survival benefit in the TOPAZ-1 trial. More scientific and clinical efforts are warranted in order to identify targetable molecular mechanisms of cholangiocarcinogenesis, develop innovative therapeutic strategies and improve our ability to stratify patients to offer them the best therapeutic strategy available.