• 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 Masuda, Daniel Ahn, Robert S Epstein, Abdel-Baset Halim, Yao Fu, Tehseen Salimi, Volker Wacheck, Yaohua He, Mei Liu, Karim A Benhadji, John A Bridgewater, and FOENIX-CCA2 Study Investigators.
• From the Department of Medicine, Stanford University School of Medicine, and the Stanford Cancer Center, Palo Alto (L.G.), and the University of California, San Francisco, San Francisco (R.K.K.) - both in California; the Mass General Cancer Center, Harvard Medical School (L.G.), and Dana-Farber Cancer Institute (T.A.A.) - both in Boston; the University of Texas M.D. Anderson Cancer Center, Houston (F.M.-B.); the Drug Development Department, Gustave Roussy, Villejuif (A.H.), and Centre Léon Bérard, Lyon (P.A.C.) - both in France; the University of Manchester and the Christie NHS Foundation Trust, Manchester (J.W.V.), and University College London Cancer Institute, London (J.A.B.) - both in the United Kingdom; National Cancer Center Hospital, Tokyo (C.M.), Kanagawa Cancer Center, Yokohama (J.F.), Hokkaido University Hospital Cancer Center, Sapporo (Y.K.), and Tohoku University Graduate School of Medicine, Sendai (K.M.) - all in Japan; the Hospital of the University of Pennsylvania (T.B.K.) and Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital (E.P.M.) - both in Philadelphia; Amsterdam University Medical Center, University of Amsterdam, Amsterdam (H.-J.K.); Asan Medical Center, University of Ulsan College of Medicine (H.-M.C.), and Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine (D.-Y.O.) - both in Seoul, South Korea; the National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (L.-T.C.); Vall d'Hebron Hospital Campus and Vall d'Hebron Institute of Oncology, University of Vic-Central University of Catalonia, Baselga Oncologic Institute, Hospital Quiron, Barcelona (J.T.); Mayo Clinic, Rochester, MN (A.M.); Johannes Gutenberg-Mainz University Medical Center, Mainz, Germany (M.M.); Mayo Clinic, Phoenix, AZ (D.A.); Epstein Health, Woodcliff Lake, NJ (R.S.E.); Taiho Oncology, Princeton, NJ (A.-B.H., T.S., V.W., Y.H., M.L., K.A.B.); and Ilumina, San Diego, CA (Y.F.).
• N. Engl. J. Med. 2023 Jan 19; 388 (3): 228239228-239.

BackgroundAlterations 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.MethodsIn 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.ResultsBetween 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.ConclusionsIn 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.).Copyright © 2023 Massachusetts Medical Society.

29 keywords...

hide…