Targeting the Fibroblast Growth Factor Receptor (FGFR) in Advanced Cholangiocarcinoma: Clinical Trial Progress and Future Considerations

Simple Summary Cholangiocarcinoma (CCA) is a cancer arising from the bile ducts. Chemotherapy has long been the standard of care for metastatic CCA, but recent clinical trials have shown that fibroblast growth factor receptor (FGFR) inhibitors are a promising new treatment in advanced CCA with documented genetic alterations in FGFR genes. This review provides an overview of the genetic features of CCA, the biology of the FGFR pathway, important FGFR inhibitor clinical trials in CCA, and future opportunities and challenges in the development of FGFR inhibitors for effective clinical use in patients with CCA. Landmark molecular profiling efforts have identified multiple targetable alterations in cholangiocarcinoma. Among the molecular-driven subsets of cholangiocarcinoma, targeting the fibroblast growth factor receptor (FGFR) has shown promise and represents the first targeted therapy to be approved in treatment-refractory, advanced cholangiocarcinoma. In this review, we provide an up-to-date overview of the clinical development of FGFR inhibitors in advanced cholangiocarcinoma. We review the FGFR pathway and discuss emerging issues including resistance to FGFR inhibitors. We end with a discussion on future considerations to optimize the potential of this class of therapeutics in advanced cholangiocarcinoma.