Breast Cancer Research and Treatment

, Volume 146, Issue 1, pp 153–162

Randomised, phase II, placebo-controlled, trial of fulvestrant plus vandetanib in postmenopausal women with bone only or bone predominant, hormone-receptor-positive metastatic breast cancer (MBC): the OCOG ZAMBONEY study

Authors

    • Division of Medical Oncology, The Ottawa Hospital Cancer CentreOttawa Hospital Research Institute and University of Ottawa
  • Brandy Cochrane
    • Ontario Clinical Oncology GroupMcMaster University
  • Gregory R. Pond
    • Ontario Clinical Oncology GroupMcMaster University
  • Nadia Califaretti
    • Grand River Regional Cancer Centre
  • Stephen K. L. Chia
    • British Columbia Cancer Agency
  • Rebecca Alexandra Dent
    • Sunnybrook Odette Cancer CentreUniversity of Toronto
  • Xinni Song
    • Division of Medical Oncology, The Ottawa Hospital Cancer CentreOttawa Hospital Research Institute and University of Ottawa
  • Andre Robidoux
    • Centre Hospitalier de L’Université de Montréal
  • Sameer Parpia
    • Ontario Clinical Oncology GroupMcMaster University
  • David Warr
    • Princess Margaret Hospital
  • Daniel Rayson
    • Nova Scotia Cancer CentreQueen Elizabeth II Health Sciences Centre
  • Kathleen I. Pritchard
    • Sunnybrook Odette Cancer CentreUniversity of Toronto
  • Mark N. Levine
    • Ontario Clinical Oncology GroupMcMaster University
Clinical trial

DOI: 10.1007/s10549-014-3015-6

Cite this article as:
Clemons, M.J., Cochrane, B., Pond, G.R. et al. Breast Cancer Res Treat (2014) 146: 153. doi:10.1007/s10549-014-3015-6

Abstract

Biomarkers of bone turnover, including urine N-telopeptide (uNTx), have been used as surrogate measures of response to bone-targeted therapies. Vascular endothelial growth factor (VEGF) levels correlate with extent of bone metastases. We assessed whether vandetanib, an inhibitor of VEGF, epidermal growth factor receptor and RET signalling, improved uNTx response when added to fulvestrant (F) in breast cancer patients with bone metastases. Postmenopausal patients with bone predominant, hormone-receptor-positive metastatic breast cancer were randomised to F (500 mg IM days 1, 15, 29, then monthly) with either vandetanib (100 mg PO OD) (FV) or placebo (FP). The primary objective was uNTx response. Secondary objectives included PFS, OS, RECIST response, pain scores and toxicity. Sixty-one patients were allocated to FV and 68 to FP. Out of 127 analyzable patients, an uNTx response occurred in 66 % for FV and 54 % for FP (p = 0.21). No difference was detected between groups for PFS; HR = 0.95 (95 % CI 0.65–1.38) or OS HR = 0.69 (95 % CI 0.37–1.31). For the 62 patients with measurable disease, clinical benefit rates were 41 and 43 %, respectively (p = 0.47). Serious adverse events were similar, 3.3 % for FV versus 5.9 % for FP. Elevated baseline uNTx (>65 nM BCE/mmol Cr) was prognostic for PFS, HR = 1.55 (95 % CI 1.04–2.30) and for OS, HR = 2.32 (95 % CI 1.25–4.33). The addition of vandetanib to fulvestrant did not improve biomarker response, PFS or OS in patients with bone metastases. Baseline bone turnover was prognostic for PFS and OS.

Keywords

Fulvestrant Vandetanib Postmenopausal Bone metastases Breast cancer

Supplementary material

10549_2014_3015_MOESM1_ESM.docx (62 kb)
Supplementary material 1 (DOCX 61 kb)

Copyright information

© Springer Science+Business Media New York 2014