Goyal, Lipika; Meric-Bernstam, Funda; Hollebecque, Antoine; Valle, Juan W; Morizane, Chigusa; Karasic, Thomas B; Abrams, Thomas A; ... FOENIX-CCA2 Study Investigators; + view all Goyal, Lipika; Meric-Bernstam, Funda; Hollebecque, Antoine; Valle, Juan W; Morizane, Chigusa; Karasic, Thomas B; Abrams, Thomas A; Furuse, Junji; Kelley, Robin K; Cassier, Philippe A; Klümpen, Heinz-Josef; Chang, Heung-Moon; Chen, Li-Tzong; Tabernero, Josep; Oh, Do-Youn; Mahipal, Amit; Moehler, Markus; Mitchell, Edith P; Komatsu, Yoshito; Masuda, Kunihiro; Ahn, Daniel; Epstein, Robert S; Halim, Abdel-Baset; Fu, Yao; Salimi, Tehseen; Wacheck, Volker; He, Yaohua; Liu, Mei; Benhadji, Karim A; Bridgewater, John A; FOENIX-CCA2 Study Investigators; - view fewer (2023) Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. New England Journal of Medicine , 388 (3) pp. 228-239. 10.1056/NEJMoa2206834.

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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. (Funded by Taiho Oncology and Taiho Pharmaceutical; FOENIX-CCA2 ClinicalTrials.gov number, NCT02052778.).

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