Futibatinib for FGFR2-rearranged intrahepatic cholangiocarcinoma
Goyal, L. Meric-Bernstam, F. Hollebecque, A. Valle, Juan W Morizane, C. Karasic, T. B. Abrams, T. A. Furuse, J. Kelley, R. K. Cassier, P. A.
Goyal, L.
Meric-Bernstam, F.
Hollebecque, A.
Valle, Juan W
Morizane, C.
Karasic, T. B.
Abrams, T. A.
Furuse, J.
Kelley, R. K.
Cassier, P. A.
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Abstract
Background: Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with FGFR-altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.
Methods: In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors). The patients received oral futibatinib at a dose of 20 mg once daily in a continuous regimen. The primary end point was objective response (partial or complete response), as assessed by independent central review. Secondary end points included the response duration, progression-free and overall survival, safety, and patient-reported outcomes.
Results: Between April 16, 2018, and November 29, 2019, a total of 103 patients were enrolled and received futibatinib. A total of 43 of 103 patients (42%; 95% confidence interval, 32 to 52) had a response, and the median duration of response was 9.7 months. Responses were consistent across patient subgroups, including patients with heavily pretreated disease, older adults, and patients who had co-occurring TP53 mutations. At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and overall survival was 21.7 months. Common treatment-related grade 3 adverse events were hyperphosphatemia (in 30% of the patients), an increased aspartate aminotransferase level (in 7%), stomatitis (in 6%), and fatigue (in 6%). Treatment-related adverse events led to permanent discontinuation of futibatinib in 2% of the patients. No treatment-related deaths occurred. Quality of life was maintained throughout treatment.
Conclusions: In previously treated patients with FGFR2 fusion or rearrangement-positive intrahepatic cholangiocarcinoma, the use of futibatinib, a covalent FGFR inhibitor, led to measurable clinical benefit.
Authors
Goyal, L.
Meric-Bernstam, F.
Hollebecque, A.
Valle, Juan W
Morizane, C.
Karasic, T. B.
Abrams, T. A.
Furuse, J.
Kelley, R. K.
Cassier, P. A.
Klümpen, H. J.
Chang, H. M.
Chen, L. T.
Tabernero, J.
Oh, D. Y.
Mahipal, A.
Moehler, M.
Mitchell, E. P.
Komatsu, Y.
Masuda, K.
Ahn, D.
Epstein, R. S.
Halim, A. B.
Fu, Y.
Salimi, T.
Wacheck, V.
He, Y.
Liu, M.
Benhadji, K. A.
Bridgewater, J. A.
Meric-Bernstam, F.
Hollebecque, A.
Valle, Juan W
Morizane, C.
Karasic, T. B.
Abrams, T. A.
Furuse, J.
Kelley, R. K.
Cassier, P. A.
Klümpen, H. J.
Chang, H. M.
Chen, L. T.
Tabernero, J.
Oh, D. Y.
Mahipal, A.
Moehler, M.
Mitchell, E. P.
Komatsu, Y.
Masuda, K.
Ahn, D.
Epstein, R. S.
Halim, A. B.
Fu, Y.
Salimi, T.
Wacheck, V.
He, Y.
Liu, M.
Benhadji, K. A.
Bridgewater, J. A.
Description
Date
2023
Publisher
Collections
Keywords
Type
Article
Citation
Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, et al. Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. The New England journal of medicine. 2023 Jan 19;388(3):228-39. PubMed PMID: 36652354. Epub 2023/01/19. eng.