Phase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR, HER2 breast cancer that had progressed during or after prior endocrine therapy.

TitlePhase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR, HER2 breast cancer that had progressed during or after prior endocrine therapy.
Publication TypeJournal Article
Year of Publication2017
AuthorsMusolino, Antonino, Mario Campone, Patrick Neven, Neelima Denduluri, Carlos H. Barrios, Javier Cortes, Kimberly Blackwell, Hatem Soliman, Zsuzsanna Kahan, Hervé Bonnefoi, Matthew Squires, Yong Zhang, Stephanie Deudon, Michael M. Shi, and Fabrice André
JournalBreast Cancer Res
Volume19
Issue1
Pagination18
Date Published2017 02 10
ISSN1465-542X
KeywordsAdult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Benzimidazoles, Breast Neoplasms, Disease Progression, Estradiol, Female, Fulvestrant, Humans, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Postmenopause, Quinolones, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Retreatment, Survival Analysis, Treatment Outcome
Abstract

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.

DOI10.1186/s13058-017-0807-8
Alternate JournalBreast Cancer Res
Original PublicationPhase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR(+), HER2(-) breast cancer that had progressed during or after prior endocrine therapy.
PubMed ID28183331
PubMed Central IDPMC5301372
Grant ListP01 CA142538 / CA / NCI NIH HHS / United States