Efficacy of futibatinib, an irreversible fibroblast growth factor receptor inhibitor, in FGFR-altered breast cancer

Abstract

Abstract The role of the fibroblast growth factor receptor (FGFR) gene alterations as therapeutic targets in breast cancer have not been well characterized. Futibatinib (TAS-120; Taiho) is a novel pan-FGFR inhibitor. We sought to determine the efficacy of futibatinib in breast cancer models with FGFR alterations. Nine breast cancer patient–derived xenografts (PDXs) with a variety of FGFR1-4 alterations and expression levels were treated with futibatinib. FGFR gene expression between patient tumors and matching PDXs was significantly correlated. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1–2.6% and 1.5–2.5%, respectively. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib.