Comparative safety of futibatinib vs pemigatinib in metastatic cholangiocarcinoma: FAERS-based analysis.

Abstract

512 Background: Fibroblast Growth Factor Receptor (FGFR) inhibitors have transformed treatment for patients with metastatic cholangiocarcinoma with FGFR2 fusion or other rearrangement. Pemigatinib and Futibatinib have shown measurable clinical benefit after progression on first line systemic therapy and are known to cause ocular toxicities and hyperphosphatemia. But comparative post-marketing safety data is limited. Using FDA Adverse Event Reporting System (FAERS) pharmacovigilance data, we evaluated real-world adverse events (AEs) associated with these agents. Methods: We queried FAERS between 2014–2025 using AERSMine to identify AEs in patients with metastatic cholangiocarcinoma treated with FGFR inhibitors. Cohorts were mutually exclusive: futibatinib (N=90) and pemigatinib (N=469). AEs were categorized as metabolic, dermatologic and ocular. Chi-Square and Fisher’s Exact tests assessed statistical significance. Results: Overall, AE distribution differed significantly (χ²=24.3, df=6, p<0.001). Hyperphosphatemia occurred in 16.7% (futibatinib) vs 13.4% (pemigatinib) while nail disorders were similar (10.0% vs 9.2%). Palmar-plantar erythrodysesthesia syndrome (PPES) was significantly higher with futibatinib than pemigatinib (18.9% vs 3.4%, p<0.001). Stomatitis trended higher with futibatinib (10.0% vs 5.3%, p= 0.095). Cataracts were reported only with futibatinib (2.2% vs 0%, p= 0.026). Retinal pigment epithelial detachment (RPED) was more frequent with pemigatinib (4.1% vs 2.2%, p= 0.553). Keratitis occurred more with futibatinib (10.0% vs 5.1%, p= 0.086) but was not statistically significant. Conclusions: Futibatinib is associated with higher incidence of dermatologic toxicities, notably PPES and keratitis. There was an increased RPED incidence with pemigatinib. These differences are clinically meaningful and should inform drug selection, toxicity monitoring, and supportive care strategies. Real-world data highlight the importance of personalized toxicity management in long-term FGFR inhibitor therapy. These findings may guide oncologists in selecting FGFR inhibitors based on patient-specific risk profiles. Adverse event comparison between futibatinib and pemigatinib. Category Adverse Event Futibatinib (N=90) Pemigatinib (N=469) Metabolic Hyperphosphatemia 15 (16.7%) 63 (13.4%) Dermatologic & Nail Toxicities Nail disorders 9 (10.0%) 43 (9.2%) Palmar-plantar erythrodysesthesia syndrome (PPES) 17 (18.9%) 16 (3.4%) Stomatitis 9 (10.0%) 25 (5.3%) Ocular Toxicities Cataract 2 (2.2%) 0 (0.0%) Retinal pigment epithelial detachment (RPED) 2 (2.2%) 19 (4.1%) Keratitis 9 (10.0%) 24 (5.1%)