Futibatinib for FGFR2 -Rearranged Intrahepatic Cholangiocarcinoma

Lipika Goyal, Funda Meric-Bernstam, Antoine Hollebecque, Juan W. Valle, Chigusa Morizane, Thomas B. Karasic, Thomas A. Abrams, Junji Furuse, Robin K. Kelley, Philippe A. Cassier, Heinz-Josef Klümpen, Heung-Moon Chang, Li-Tzong Chen, Josep Tabernero, Do-Youn Oh, Amit Mahipal, Markus Moehler, Edith P. Mitchell, Yoshito Komatsu, Kunihiro MasudaDaniel Ahn, Robert S. Epstein, Abdel-Baset Halim, Yao Fu, Tehseen Salimi, Volker Wacheck, Yaohua He, Mei Liu, Karim A. Benhadji, John A. Bridgewater

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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.
Original languageEnglish
Pages (from-to)228-239
Number of pages12
JournalNew England journal of medicine
Issue number3
Publication statusPublished - 2023


  • Cancer
  • Gastroenterology
  • Gastrointestinal Tract Cancer
  • Genetics
  • Hematology/Oncology
  • Treatments in Oncology

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