VEGF-A levels in bevacizumab-treated breast cancer patients: a systematic review and meta-analysis

Bevacizumab may improve outcomes of patients with breast cancer, but the absence of an established biomarker hampers patient selection and researchers´ ability to demonstrate a clear survival benefit. Its putative target, circulating VEGF-A, emerged as the main candidate and we sought to identify th...

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Bibliographic Details
Published in:Breast cancer research and treatment 2015-06, Vol.151 (3), p.481-489
Main Authors: dos Santos, Lucas Vieira, Cruz, Marcelo Rocha, Lima Lopes, Gilberto de, Lima, Joao Paulo da Silveira Nogueira
Format: Article
Language:English
Subjects:
Analysis
Angiogenesis Inhibitors - administration & dosage
Angiogenesis Inhibitors - therapeutic use
Antineoplastic agents
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bevacizumab - administration & dosage
Bevacizumab - therapeutic use
Biomarkers
Breast cancer
Breast Neoplasms - blood
Breast Neoplasms - drug therapy
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Cancer patients
Cancer research
Cancer therapies
Care and treatment
Chemotherapy
Development and progression
Female
Humans
Medicine
Medicine & Public Health
Neoplasm Staging
Oncology
Prognosis
Proportional Hazards Models
Randomized Controlled Trials as Topic
Review
Survival Analysis
Systematic review
Treatment Outcome
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - blood
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Summary:Bevacizumab may improve outcomes of patients with breast cancer, but the absence of an established biomarker hampers patient selection and researchers´ ability to demonstrate a clear survival benefit. Its putative target, circulating VEGF-A, emerged as the main candidate and we sought to identify the relationship between VEGF-A levels and outcomes through systematic review. We searched electronic databases and meeting proceedings for randomized controlled trials (RCTs) comparing the addition of bevacizumab to standard chemotherapy for breast cancer. RCTs were included if outcomes were presented separately according to VEGF-A plasma levels. Random-effects model were applied to calculate the pooled hazard ratios for progression-free survival, 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 the interaction test. Heterogeneity was calculated using χ 2 test ( I 2 ). Three trials enrolled a total of 3748 patients. 1713 patients had baseline VEGF-A levels in plasma available for assessment and were included. One trial added bevacizumab in the adjuvant setting ( N  = 2591) and two on first-line metastatic disease with taxane-based therapy ( N  = 1160) There was no interaction between VEGF-A levels and study setting (adjuvant vs. first line therapy). Bevacizumab improved PFS of patients with above median VEGF-A plasma levels (HR 0.56; 95 % CI 0.43–0.73; P  
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-015-3410-7