TY - JOUR
T1 - Futibatinib for FGFR2 -Rearranged Intrahepatic Cholangiocarcinoma
AU - Goyal, Lipika
AU - Meric-Bernstam, Funda
AU - Hollebecque, Antoine
AU - Valle, Juan W.
AU - Morizane, Chigusa
AU - Karasic, Thomas B.
AU - Abrams, Thomas A.
AU - Furuse, Junji
AU - Kelley, Robin K.
AU - Cassier, Philippe A.
AU - Klümpen, Heinz Josef
AU - Chang, Heung Moon
AU - Chen, Li Tzong
AU - Tabernero, Josep
AU - Oh, Do Youn
AU - Mahipal, Amit
AU - Moehler, Markus
AU - Mitchell, Edith P.
AU - Komatsu, Yoshito
AU - Masuda, Kunihiro
AU - Ahn, Daniel
AU - Epstein, Robert S.
AU - Halim, Abdel Baset
AU - Fu, Yao
AU - Salimi, Tehseen
AU - Wacheck, Volker
AU - He, Yaohua
AU - Liu, Mei
AU - Benhadji, Karim A.
AU - Bridgewater, John A.
N1 - Publisher Copyright:
© 2023 Massachusetts Medical Society.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Cancer
KW - Gastroenterology
KW - Gastrointestinal Tract Cancer
KW - Gastrointestinal Tract Cancer
KW - Genetics
KW - Hematology/Oncology
KW - Treatments in Oncology
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U2 - 10.1056/NEJMoa2206834
DO - 10.1056/NEJMoa2206834
M3 - Article
C2 - 36652354
AN - SCOPUS:85149023684
SN - 0028-4793
VL - 388
SP - 228
EP - 239
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 3
ER -