Pharmacologic features, clinical applications, and drug safety evaluation of futibatinib in the treatment of biliary tract cancer (BTC).

INTRODUCTION: Futibatinib is a small, potent, covalent, irreversible fibroblast growth factor receptor (FGFR) 1-4 inhibitor that has been added as a new standard of care for previously treated unresectable and/or advanced FGFR2 fusion/rearrangement-positive BTC. FGFR2 fusions/rearrangements play a key role in BTC survival, proliferation, invasion, and development of distant metastasis. The inhibition of this pathway is an important target in the treatment of BTC. AREAS COVERED: The article covers the development of futibatinib for the treatment of refractory unresectable/advanced BTC, its mechanism of action, and key pharmacodynamic/pharmacokinetic data with a focus on the safety profile. Data are based on published clinical trials, pooled analysis, and retrospective studies indexed in PubMed (2010-2024). EXPERT OPINION: Futibatinib is an FDA and EMA approved FGFR2 inhibitor for the treatment of patients with refractory BTC with FGFR2 fusions/rearrangements. Ongoing drug development strategies are centered on designing new FGFR2 fusion inhibitors able to overcome on-target and off-target resistances coupled with a high target selectivity to spare the most common treatment-related adverse events (hyperphosphatemia, stomatitis, alopecia, nail toxicity, skin reactions, eye toxicity).