Data mining and safety analysis of FGFR tyrosine kinase inhibitors based on the FAERS database.

Fibroblast growth factor receptor tyrosine kinase inhibitors (FGFR-TKIs), including erdafitinib, pemigatinib, and futibatinib, are a promising class of therapies for FGFR-driven cancers. While their efficacy is established in clinical trials, real-world safety data remain limited. This study leveraged post-marketing data from the FDA Adverse Event Reporting System (FAERS) between the second quarter of 2019 and the third quarter of 2024 to evaluate the safety profiles of FGFR-TKIs through disproportionality analysis. A total of 1,629 reports were included (erdafitinib: 982, pemigatinib: 558, futibatinib: 89). The most frequently reported adverse events (AEs) belonged to general disorders, gastrointestinal disorders, and skin and subcutaneous tissue disorders. Notably, several novel AEs not previously identified in clinical trials or drug labels were detected, including corneal thinning associated with erdafitinib, fluid intake reduced with pemigatinib, and blood magnesium decreased with futibatinib. Time-to-onset analysis revealed that delayed median AE onset for erdafitinib (56.5 days) compared to pemigatinib (29 days) and futibatinib (25 days), although all exhibited early failure-type patterns. Subgroup analysis indicated an increased risk of death in futibatinib-treated patients aged < 65 years. These findings offer critical insights beyond clinical trials, informing oncologists of emerging safety concerns associated with FGFR-TKIs in real-world settings.