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

Autor:	Vogel A; Hannover Medical School, Hannover, Germany; Toronto General Hospital, Toronto; Princess Margaret Cancer Centre, Toronto, Canada. Electronic address: vogela@me.com., Sahai V; University of Michigan, Ann Arbor, USA., Hollebecque A; Gustave Roussy Cancer Center, Paris, France., Vaccaro GM; Providence Cancer Center, Portland, USA., Melisi D; Università degli studi di Verona, Verona, Italy., Al Rajabi RM; University of Kansas Medical Center, Kansas City., Paulson AS; Baylor University Medical Center, Dallas., Borad MJ; Mayo Clinic Cancer Center, Phoenix., Gallinson D; Morristown Memorial Hospital, Morristown., Murphy AG; Johns Hopkins University School of Medicine, Baltimore, USA., Oh DY; Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea., Dotan E; Fox Chase Cancer Center, Philadelphia., Catenacci DV; University of Chicago Medicine, Chicago, USA., Van Cutsem E; University Hospitals Gasthuisberg, Leuven & University of Leuven, Leuven, Belgium., Lihou CF; Incyte Corporation, Wilmington, USA., Zhen H; Incyte Corporation, Wilmington, USA., Veronese ML; Incyte International Biosciences Sàrl, Morges, Switzerland., Abou-Alfa GK; Memorial Sloan Kettering Cancer Center, New York; Weill Medical College at Cornell University, New York, USA; Trinity College Dublin School of Medicine, Dublin, Ireland.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2024 Jun; Vol. 9 (6), pp. 103488. Date of Electronic Publication: 2024 Jun 04.
DOI:	10.1016/j.esmoop.2024.103488
Abstrakt:	Background: 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. Patients and Methods: 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. Results: 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. Conclusions: 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. (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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