Introduction: The Targeted Therapy Landscape in Cholangiocarcinoma
Cholangiocarcinoma (CCA), a group of rare but aggressive malignancies arising from the biliary tree, has historically been associated with a poor prognosis and limited therapeutic options beyond first-line gemcitabine-based chemotherapy. However, the advent of precision medicine has shifted the paradigm, particularly for intrahepatic cholangiocarcinoma (iCCA), where approximately 40% of patients harbor actionable genetic alterations. Among the most significant of these are fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements, which occur in nearly 10-20% of patients with iCCA.
Erdafitinib, a potent oral pan-FGFR tyrosine kinase inhibitor, was initially approved for the treatment of locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 alterations. Given its broad activity across multiple FGFR isoforms, its efficacy in other FGFR-driven malignancies, specifically CCA, has been a subject of intense investigation. This article explores the findings of a recently published pooled analysis of the RAGNAR and LUC2001 studies, which evaluated erdafitinib in patients with advanced or metastatic CCA harboring FGFR alterations.
