Phase II study of the multikinase inhibitor dovitinib (TKI258) or placebo in combination with fulvestrant in postmenopausal, endocrine resistant HER2-/HR+ breast cancer.

TPS1148 Background: Overcoming endocrine resistance is a critical goal in the treatment of hormone receptor−positive (HR+) breast cancer. Molecular mechanisms associated with endocrine resistance include adaptive “cross-talk” between the estrogen receptor and the fibroblast growth factor receptor (FGFR). Up to 8% of HR+/HER2- breast cancer patients (pts) have amplification of the FGFR1 gene, which is associated with resistance to endocrine therapy but can be overcome via FGFR1 inhibition in preclinical models. Dovitinib is a potent FGF, VEGF, and PDGF receptor tyrosine kinase inhibitor that demonstrated antitumor activity in heavily pretreated breast cancer pts with FGF pathway amplification (FGFR1, FGFR2, or ligand FGF3; Andre et al, ASCO 2011). Dovitinib may reverse resistance to endocrine therapy related to FGF-pathway amplification and is studied here to determine if it can improve outcomes when combined with fulvestrant. Methods: Postmenopausal HER2-/HR+ locally advanced or metastatic breast cancer p...