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

  • Mark J. Clemons
  • Brandy Cochrane
  • Gregory R. Pond
  • Nadia Califaretti
  • Stephen K. L. Chia
  • Rebecca Alexandra Dent
  • Xinni Song
  • Andre Robidoux
  • Sameer Parpia
  • David Warr
  • Daniel Rayson
  • Kathleen I. Pritchard
  • Mark N. Levine
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

FulvestrantVandetanibPostmenopausalBone metastasesBreast 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

Authors and Affiliations

  • Mark J. Clemons
    • 1
  • Brandy Cochrane
    • 2
  • Gregory R. Pond
    • 2
  • Nadia Califaretti
    • 3
  • Stephen K. L. Chia
    • 4
  • Rebecca Alexandra Dent
    • 5
  • Xinni Song
    • 1
  • Andre Robidoux
    • 6
  • Sameer Parpia
    • 2
  • David Warr
    • 7
  • Daniel Rayson
    • 8
  • Kathleen I. Pritchard
    • 5
  • Mark N. Levine
    • 2
  1. 1.Division of Medical Oncology, The Ottawa Hospital Cancer CentreOttawa Hospital Research Institute and University of OttawaOttawaCanada
  2. 2.Ontario Clinical Oncology GroupMcMaster UniversityHamiltonCanada
  3. 3.Grand River Regional Cancer CentreKitchenerCanada
  4. 4.British Columbia Cancer AgencyVancouverCanada
  5. 5.Sunnybrook Odette Cancer CentreUniversity of TorontoTorontoCanada
  6. 6.Centre Hospitalier de L’Université de MontréalMontrealCanada
  7. 7.Princess Margaret HospitalTorontoCanada
  8. 8.Nova Scotia Cancer CentreQueen Elizabeth II Health Sciences CentreHalifaxCanada