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Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma.
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.
Afiliación
  • Goyal L; 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 Canc
  • Meric-Bernstam F; 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 Canc
  • Hollebecque A; 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 Canc
  • Valle JW; 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 Canc
  • Morizane C; 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 Canc
  • Karasic TB; 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 Canc
  • Abrams TA; 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 Canc
  • Furuse J; 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 Canc
  • Kelley RK; 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 Canc
  • Cassier PA; 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 Canc
  • Klümpen HJ; 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 Canc
  • Chang HM; 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 Canc
  • Chen LT; 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 Canc
  • Tabernero J; 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 Canc
  • Oh DY; 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 Canc
  • Mahipal A; 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 Canc
  • Moehler M; 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 Canc
  • Mitchell EP; 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 Canc
  • Komatsu Y; 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 Canc
  • Masuda K; 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 Canc
  • Ahn D; 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 Canc
  • Epstein RS; 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 Canc
  • Halim AB; 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 Canc
  • Fu Y; 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 Canc
  • Salimi T; 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 Canc
  • Wacheck V; 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 Canc
  • He Y; 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 Canc
  • Liu M; 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 Canc
  • Benhadji KA; 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 Canc
  • Bridgewater JA; 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 Canc
N Engl J Med ; 388(3): 228-239, 2023 01 19.
Article en En | MEDLINE | ID: mdl-36652354
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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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de los Conductos Biliares / Conductos Biliares Intrahepáticos / Colangiocarcinoma / Inhibidores de Proteínas Quinasas / Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos / Antineoplásicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Aged / Humans Idioma: En Revista: N Engl J Med Año: 2023 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de los Conductos Biliares / Conductos Biliares Intrahepáticos / Colangiocarcinoma / Inhibidores de Proteínas Quinasas / Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos / Antineoplásicos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Aged / Humans Idioma: En Revista: N Engl J Med Año: 2023 Tipo del documento: Article