福巴替尼的功效和副作用？

forbatinib

It is an oral, irreversible, highly selective fibroblast growth factor receptor (FGFR) 1-4 inhibitor with potential preclinical activity against tumors with FGFR aberrations.

Forbatinib/Futibatinib demonstrated an objective response rate (ORR) of 13.7% across a broad spectrum of tumors with known and previously uncharacterized FGFR1-3 abnormalities, such as cholangiocarcinoma and gastric, urothelial, central nervous system, head and neck, and breast cancer.

forbatinib

Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets in intrahepatic cholangiocarcinoma. Futibatinib is a next-generation covalently binding FGFR1-4 inhibitor that has demonstrated antitumor activity in patients with FGFR-altered tumors and has strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.

In a multinational, open-label, single-arm, phase 2 study, 103 patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma who had disease progression after one or more prior systemic therapies were enrolled.

Patients received oral fortibatinib at a dose of 20 mg once daily, and 43 of 103 patients responded, with a median duration of response of 9.7 months. Responses were consistent across patient subgroups, including those with severe pre-treatment disease, the elderly, and those with concurrent TP53 mutations.

At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and the overall survival was 21.7 months.

forbatinib

Common treatment-related grade 3 adverse events included hyperphosphatemia (30% of patients), increased aspartate aminotransferase levels (7%), stomatitis (6%), and fatigue (6%).

Side effects such as musculoskeletal pain, constipation, diarrhea, nausea, loss of appetite, fatigue, dry mouth, alopecia, stomatitis, abdominal pain, joint pain, etc. may also occur. Treatment-related adverse events led to permanent discontinuation of flutibatinib in 2% of patients.

References:

Goyal L, Meric-Bernstam F, Hollebecque A, Valle JW, Morizane C, Karasic TB, Abrams TA, Furuse J, Kelley RK, Cassier PA, Klümpen HJ, Chang HM, Chen LT, Tabernero J, Oh DY, Mahipal A, Moehler M, Mitchell EP, Komatsu Y, Masuda K, Ahn D, Epstein RS, Halim AB, Fu Y, Salimi T, Wacheck V, He Y, Liu M, Benhadji KA, Bridgewater JA; FOENIX-CCA2 Study Investigators. Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. N Engl J Med. 2023 Jan 19;388(3):228-239. doi: 10.1056/NEJMoa2206834. PMID: 36652354.

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