An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202

• Published in: ESMO open Vol. 9; no. 6; p. 103488
• Main Authors: Vogel, A., Sahai, V., Hollebecque, A., Vaccaro, G.M., Melisi, D., Al Rajabi, R.M., Paulson, A.S., Borad, M.J., Gallinson, D., Murphy, A.G., Oh, D.-Y., Dotan, E., Catenacci, D.V., Van Cutsem, E., Lihou, C.F., Zhen, H., Veronese, M.L., Abou-Alfa, G.K.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2024; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms - drug therapy; Cholangiocarcinoma - drug therapy; Female; fibroblast growth factor receptor; Humans; intrahepatic cholangiocarcinoma; Male; Middle Aged; Morpholines; next-generation sequencing; Original Research; pemigatinib; precision medicine; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Pyrroles; Receptor, Fibroblast Growth Factor, Type 2; targeted therapy; targeted therapy; precision medicine; next-generation sequencing; fibroblast growth factor receptor; pemigatinib; intrahepatic cholangiocarcinoma
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2024.103488

Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period. The multicenter, open-label, single-arm, phase II FIGHT-202 study enrolled patients ≥18 years old with previously treated advanced/metastatic CCA with FGFR2 fusions or rearrangements (cohort A), other FGF/FGFR alterations (cohort B), or no FGF/FGFR alterations (cohort C). Patients received once-daily oral pemigatinib 13.5 mg in 21-day cycles (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) in cohort A assessed as per RECIST v1.1 by an independent review committee; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. FIGHT-202 enrolled 147 patients (cohort A, 108; cohort B, 20; cohort C, 17; unconfirmed FGF/FGFR alterations, 2). By final analysis, 145 (98.6%) had discontinued treatment due to progressive disease (71.4%), withdrawal by patient (8.2%), or adverse events (AEs; 6.8%). Median follow-up was 45.4 months. The ORR in cohort A was 37.0% (95% confidence interval 27.9% to 46.9%); complete and partial responses were observed in 3 and 37 patients, respectively. Median DOR was 9.1 (6.0-14.5) months; median PFS and OS were 7.0 (6.1-10.5) months and 17.5 (14.4-22.9) months, respectively. The most common treatment-emergent AEs (TEAEs) were hyperphosphatemia (58.5%), alopecia (49.7%), and diarrhea (47.6%). Overall, 15 (10.2%) patients experienced TEAEs leading to pemigatinib discontinuation; intestinal obstruction and acute kidney injury (n = 2 each) occurred most frequently. Pemigatinib demonstrated durable response and prolonged OS with manageable AEs in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in the extended follow-up period of FIGHT-202. •FIGHT-202 evaluated pemigatinib in patients with previously treated, advanced/metastatic CCA with FGFR2 rearrangements.•Median follow-up was 45.4 months; pemigatinib demonstrated an ORR of 37% and a median DOR of 9.1 months.•Median PFS and OS were 7.0 and 17.5 months, respectively.•AEs with pemigatinib treatment were manageable; during extended follow-up, no new safety signals were identified.•The importance of tumor molecular profiling and pemigatinib efficacy in CCA with FGFR2 fusions/rearrangements are described.