BACKGROUND: Overexpression of fibroblast growth factor receptor 1 (FGFR1), found 
in ≤8% of hormone receptor-positive (HR+), human epidermal growth factor 
receptor 2-negative (HER2-) breast cancer cases, is correlated with decreased 
overall survival and resistance to endocrine therapy (ET). Dovitinib, a potent 
FGFR inhibitor, has demonstrated antitumor activity in heavily pretreated 
patients with FGFR pathway-amplified breast cancer.
METHODS: In this randomized, placebo-controlled phase II trial, we evaluated 
whether the addition of dovitinib to fulvestrant would improve outcomes in 
postmenopausal patients with HR+, HER2- advanced breast cancer that had 
progressed during or after prior ET. Patients were stratified by FGF pathway 
amplification and presence of visceral disease, and they were randomized 1:1 to 
receive fulvestrant plus dovitinib or placebo. The primary endpoint was 
progression-free survival (PFS).
RESULTS: From 15 May 2012 to 26 November 2014, 97 patients from 36 centers were 
enrolled. The frequency of FGF pathway amplification was lower than anticipated, 
and the study was terminated early owing to slow accrual of patients with FGF 
pathway amplification. The median PFS (95% CI) was 5.5 (3.8-14.0) months vs 5.5 
(3.5-10.7) months in the dovitinib vs placebo arms, respectively (HR, 0.68; did 
not meet predefined efficacy criteria). For the FGF pathway-amplified subgroup 
(n = 31), the median PFS (95% CI) was 10.9 (3.5-16.5) months vs 5.5 (3.5-16.4) 
months in the dovitinib vs placebo arms, respectively (HR, 0.64; met the 
predefined superiority criteria). Frequently reported adverse events in the 
dovitinib (diarrhea, nausea, vomiting, asthenia, and headache) and placebo 
(diarrhea, fatigue, nausea, and asthenia) arms were mostly low grade.
CONCLUSIONS: The safety profile of dovitinib plus fulvestrant was consistent 
with the known safety profile of single-agent dovitinib. Dovitinib in 
combination with fulvestrant showed promising clinical activity in the FGF 
pathway-amplified subgroup. However, the data reported herein should be 
interpreted with caution, given that fewer PFS events occurred in the FGF 
pathway-amplified patients than was expected and that an effect of dovitinib 
regardless of FGR pathway amplification status cannot be excluded, because the 
population was smaller than expected.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01528345 . Registered 31 
January 2012.