Pemigatinib: Hot topics behind the first approval of a targeted therapy in cholangiocarcinoma

Cholangiocarcinoma (CCA) includes a heterogeneous group of malignancies with limited treatment options. Despite recent advances in medical oncology, the prognosis of CCA patients with metastatic disease remains poor, with a median overall survival of less than a year. In the last decade, notable efforts have been made by the CCA medical community in an attempt to improve clinical outcomes of patients, with the development of molecularly targeted therapies in this setting. Among these treatments, the fibroblast growth factor receptor (FGFR) 2 inhibitor pemigatinib has received accelerated approval in April 2020 by the US Food and Drug Administration (FDA) in CCA patients harboring FGFR2 gene fusions or other rearrangements, on the basis of the results of the FIGHT-202 trial, and thus, representing the first molecularly targeted therapy to be approved for the treatment of CCA. However, several issues remain, including the emergence of polyclonal mutations determining resistance to pemigatinib, the identification of biomarkers predictive of response, and the knowledge gaps regarding the role of other FGFR gene aberrations. This review aims to provide an overview of recent development of pemigatinib, especially focusing on the results of the pivotal FIGHT-202 trial, the approval of this FGFR inhibitor, and the future challenges concerning the use of FGFR-directed treatments in CCA patients.