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

Abstract

Aim

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.

Methods

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).

Results

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.

Conclusions

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

Disclosure

All authors have declared no conflicts of interest.