Precision oncology targeting FGFRs: A systematic review on pre-clinical activity and clinical outcomes of pemigatinib
Ludovica Gnagni, Ilary Ruscito, Ilaria Grazia Zizzari, Marianna Nuti, Chiara Napoletano, Aurelia Rughetti
Abstract
Fibroblast Growth Factor Receptors (FGFRs) are emerging as key factors involved in tumorigenesis, tumor microenvironment remodeling and acquired resistance to targeted therapies. Pemigatinib is a Tyrosine-Kinase Inhibitor that selectively targets aberrant FGFR1, FGFR2 and FGFR3. Pemigatinib is now approved for advanced-stage cholangiocarcinoma (CCA) but data suggests that other tumor histotypes exhibit FGFR alterations, thus hypothesizing its potential efficacy in other cancer settings. The present systematic review, based on PRISMA guidelines, aims to synthetize and critically interpret the results of all available preclinical and clinical evidence regarding Pemigatinib use in cancer. In April 2024, an extensive search was performed in PubMed, MEDLINE, and Scopus databases using the keyword "Pemigatinib". Twenty-seven studies finally met all inclusion criteria. The promising results emerging from Pemigatinib preclinical and clinical studies pave the way for Pemigatinib extension to multiple solid cancer settings. • FGFRs promote tumorigenesis, microenvironment remodeling, and immune modulation. • Pemigatinib is a potent anti-FGFRs TKI now approved in advanced cholangiocarcinoma. • Many clinical trials are ongoing to assess Pemigatinib efficacy in other cancers. • This is a systematic review performed following PRISMA guidelines in April 2024. • This study summaries all preclinical and clinical results on Pemigatinib in cancer.