374P - VEGF-A level as a predictor of bevacizumab benefit for breast cancer: systematic review with meta-analysis

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Translational Research
Presenter Joao Paulo Lima
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors J.P. Lima1, D.N. Rodrigues2, F.M. Carcano3, M.R.S. Cruz4, L.V. Dos Santos5
  • 1Medical Oncology Department, Royal Marsden Hospital, sm2 5pt - Surrey/GB
  • 2Prostate Cancer Targeted Therapy Group And Drug Development Unit, Institute of Cancer Research, sm2 5pt - Surrey/GB
  • 3Medical Oncology Department, Barretos Cancer Hospital, Barretos/BR
  • 4Medical Oncology Department, Centro Oncológico Antonio Ermirio de Moraes Hospital Sao jose, Sao Paulo/BR
  • 5Medical Oncology Department, Hemomed Institute, Sao Paulo/BR



Bevacizumab lacks any potential biomarker of benefit, precluding its optimal use for breast cancer therapy. Among the putative candidates, the serum levels of vascular endothelial growth factor-A (VEGF-A) - a target of bevacizumab - has recently called attention as a promising marker. We sought to evaluate the role of VEGF-A levels as a biomarker.


We searched electronic databases and meeting proceeding for randomised controlled trials (RCTs) comparing the addition of bevacizumab to standard chemotherapy. RCTs were included if outcomes of high and low VEGF-A serum breast cancer patients were presented. Random-effects model were applied to calculate the pooled hazard ratios for event-free survival (EFS), comprising disease recurrence, progression or any-cause death, and overall survival (OS), with respective confidence intervals (95% CI). High and low VEGF-A levels subgroups followed each trial definition, and results were compared using interaction test. Heterogeneity was calculated using Chi-squared test (I2).


Three trials enrolled a total of 3748 patients, with 1713 patients with VEGF-A serum available for assessment, were included. One trial added bevacizumab in adjuvant setting (N = 2591, 1155 for biomarker evaluation) and two as first-line therapy (N = 1157, 558 for biomarker evaluation). Bevacizumab improved EFS of patients with above median VEGF-A serum levels (HR: 0.62; 95% CI 0.49–0.79; P < 0.001; I2 = 11%), but not those with below median VEGF-A levels (EFS 0.89; 95% CI 0.71–1.11; P = 0.98; I2 = 17%), with relevant differences between these two groups, P for interaction = 0.03. There was no interaction between VEGF-A levels and the study population (adjuvant versus first line therapy). OS data was not available, and therefore data could not be pooled.


The need for a marker of benefit of this expensive therapy medication is an unmet need and better patient selection can improve outcomes and resource use. Serum VEGF-A levels may be a promising marker of bevacizumab activity in breast cancer, either in palliative or adjuvant scenario and further assessment of bevacizumab use in breast cancer should focus on VEGF-A measurement


All authors have declared no conflicts of interest.