A drug safety evaluation of pemigatinib for advanced cholangiocarcinoma

Introduction: Pemigatinib is a selective small-molecule inhibitor of the fibroblast growth factor receptor (FGFR) 1–3. FGFR is associated with increased cell division, proliferation, and survival. Inhibition of this receptor is an effective treatment against tumors driven by activated fusions in FGFR2. Areas Covered: The drug was first evaluated in patients with advanced solid tumors and demonstrated a manageable safety profile, with the most common adverse events being oscillations in blood phosphate levels, fatigue, gastrointestinal symptoms, and skin and ocular toxicities. Pemigatinib was further evaluated in a phase II cohort study of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring FGFR2 genomic alterations. After a median follow-up of 17.8 months, the objective response rate in patients with tumors harboring FGFR2 fusions or rearrangements was 35.5% (95% CI, 26.5–45.4). Based on these results, the FDA granted accelerated approval on 17 April 2020, to pemigatinib, for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or another rearrangement. Articles selected for this review were based on reported studies indexed in PubMed (2010–2023). Expert Opinion: Future perspectives in the treatment of FGFR2 fused cholangiocarcinoma include the evaluation of pemigatinib in previously untreated patients and possible active combinations or sequencing strategies with other drugs.