Safety Profile and Adverse Event Management for Futibatinib, An Irreversible FGFR1–4 Inhibitor: Pooled Safety Analysis of 469 Patients
Menée à partir des données de 3 essais de phase I ou II incluant un total de 469 patients atteints d'une tumeur non résécable et/ou de stade métastatique, dont un cholangiocarcinome intrahépatique, cette étude analyse la toxicité du futibatinib (un inhibiteur ciblant FGFR1-4) et évalue la prise en charge des effets indésirables
Purpose: Futibatinib, a covalently-binding inhibitor of FGFR1–4 gained approval for the treatment of refractory, advanced intrahepatic cholangiocarcinoma (iCCA) harboring an FGFR2 fusion/other rearrangement. An integrated analysis was performed to evaluate safety and provide guidance on management of futibatinib-associated adverse events (AE) in patients with unresectable/metastatic tumors, including iCCA. Patients and Methods: Data from three global phase I or II studies of futibatinib (NCT02052778; JapicCTI-142552) were pooled. AEs were graded per NCI CTCAE v4.03, where applicable. Safety was analyzed for patients receiving any futibatinib starting dose (overall population) and in those receiving the approved starting dose of 20 mg once every day. Results: In total, 469 patients with one of 33 known tumor types were analyzed, including 318 patients who received futibatinib 20 mg every day. AEs of clinical interest (AECI; any grade/grade
≥
3) in the overall population included hyperphosphatemia (82%/19%), nail disorders (27%/1%), hepatic AEs (27%/11%), stomatitis (19%/3%), palmar-plantar erythrodysesthesia syndrome (PPES; 13%/3%), rash (9%/0%), retinal disorders (8%/0%), and cataract (4%/1%). Median time to onset of grade
≥
3 AECIs ranged from 9 days (hyperphosphatemia) to 125 days (cataract). Grade
≥
3 hyperphosphatemia, hepatic AEs, PPES, and nail disorders resolved to grade
≤
2 within a median of 7, 7, 8, and 28 days, respectively. Discontinuations due to treatment-related AEs were rare (2%), and no treatment-related deaths occurred. AE management included phosphate-lowering medication and dose adjustments. Conclusions: Futibatinib showed a consistent and manageable safety profile across patients with various tumor types. AECIs were mostly reversible with appropriate clinical management.