Biomarkers to predict the clinical efficacy of bevacizumab in cancer.
Bevacizumab is a monoclonal antibody against vascular endothelial growth factor that has antiangiogenic activity and improves progression-free survival in many solid malignancies when combined with cytotoxic chemotherapy, but has little effect on overall survival. Despite the effects of this drug in unselected patients, the Response Evaluation Criteria in Solid Tumours are suboptimum to predict benefit. Additionally, tumours show inherent and emerging resistance to regimens that include bevacizumab. The ability to target therapy towards well selected subgroups of patients would increase the likelihood of benefits and would improve cost-effectiveness and therapeutic outcomes. In this review we discuss putative clinical, radiological, and molecular markers of bevacizumab efficacy, derived from data obtained in clinical trials. Current evidence indicates some predictive value for hypertension, vascular imaging, and polymorphisms affecting components of the vascular endothelial growth factor pathway in patients receiving bevacizumab. Many questions relating to these and other surrogate biomarkers, however, remain unanswered and their clinical usefulness has yet to be proven.
Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. adrianjubb@gmail.com
Adrian M
AM
Jubb
Adrian L
AL
Harris
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab