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Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma

A phase 2 trial demonstrates the benefits and safety of futibatinib in previously treated patients with fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement–positive intrahepatic cholangiocarcinoma. Alterations in this gene “have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis,” the authors write. “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.”

The multinational, open-label, single-group, phase 2 study included patients with unresectable or metastatic FGFR2 fusion–positive or FGFR2 rearrangement–positive intrahepatic cholangiocarcinoma and disease progression after 1 or more previous lines of systemic therapy (excluding FGFR inhibitors). All patients received oral futibatinib 20 mg once daily in a continuous regimen.

Based on a primary endpoint of objective response (partial or complete response), the study showed: “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.”

Source: New England Journal of Medicine