Abstract
BACKGROUND: Cholangiocarcinoma (CCA) is an aggressive bile duct cancer with limited therapeutic options and poor prognosis. pemigatinib, a selective FGFR inhibitor, has emerged as a promising targeted therapy for CCA patients harboring FGFR2 fusions or rearrangements. This systematic review evaluated the safety and efficacy of pemigatinib in this patient population. METHODS: A comprehensive systematic review was conducted across PubMed, Scopus, Embase, Cochrane Library, and Web of Science to identify studies investigating pemigatinib in CCA patients. Five studies involving a total of 459 patients met the inclusion criteria. RESULTS: Pemigatinib demonstrated an overall objective response rate (ORR) of 43.2%, with a complete response (CR) achieved in 3% of patients. Stable disease was observed in 36.9% of patients, while 14.9% experienced disease progression. Median progression-free survival (PFS) varied across studies, due to differences in patient cohorts. The most common adverse effects (AEs) included hyperphosphatemia (48%), diarrhea (28.6%), fatigue (33%), and dry eyes (20.1%). CONCLUSIONS: This systematic review suggests that pemigatinib has modest therapeutic efficacy in CCA patients, with a considerable proportion achieving disease control. However, the ORR of less than 50% highlights the potential need for combination or sequential therapies to improve outcomes. Close monitoring and management of AEs, particularly hyperphosphatemia, are crucial for optimizing treatment. Further large-scale randomized trials and research are warranted to identify predictive biomarkers and optimize pemigatinib-based treatment strategies for CCA patients with FGFR2 alterations.