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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.
- Source :
- Breast Cancer Research; 2/10/2017, Vol. 19, p1-14, 14p, 1 Diagram, 3 Charts, 2 Graphs
- Publication Year :
- 2017
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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.<bold>Conclusions: </bold>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.<bold>Trial Registration: </bold>ClinicalTrials.gov identifier: NCT01528345 . Registered 31 January 2012. [ABSTRACT FROM AUTHOR]
- Subjects :
- FIBROBLAST growth factor receptors
HORMONE receptors
HORMONE therapy
BREAST cancer
PROGRESSION-free survival
PROTEIN metabolism
ANTINEOPLASTIC agents
BREAST tumors
CELL receptors
COMPARATIVE studies
ESTRADIOL
HETEROCYCLIC compounds
RESEARCH methodology
MEDICAL cooperation
METASTASIS
QUINOLONE antibacterial agents
REOPERATION
RESEARCH
RESEARCH funding
SURVIVAL analysis (Biometry)
TUMOR classification
EVALUATION research
RANDOMIZED controlled trials
TREATMENT effectiveness
POSTMENOPAUSE
DISEASE progression
Subjects
Details
- Language :
- English
- ISSN :
- 14655411
- Volume :
- 19
- Database :
- Complementary Index
- Journal :
- Breast Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 121416646
- Full Text :
- https://doi.org/10.1186/s13058-017-0807-8