Incidence and risk of significantly raised blood pressure in cancer patients treated with bevacizumab: an updated meta-analysis

Eur J Clin Pharmacol. 2010 Aug;66(8):813-21. doi: 10.1007/s00228-010-0815-4. Epub 2010 Apr 17.

Abstract

Purpose: Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor. The aim of this study was to gain a better understanding of the overall incidence and risk of significantly raised blood pressure in cancer patients who receive bevacizumab therapy.

Methods: We performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, Embase, and American Society of Clinical Oncology conferences. Overall incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. The primary clinical endpoint was significantly raised blood pressure (grade 3 or above).

Results: A total of 12,949 cancer patients with a variety of solid tumors from 19 RCTs were included in our meta-analysis. The overall incidence of significantly raised blood pressure was 8% (95% CI 6-10%) among patients receiving bevacizumab. Bevacizumab treatment was associated with a statistically significant increased risk of developing significantly raised blood pressure (RR 5.38, 95% CI 3.63-7.97). The RRs of significantly raised blood pressure in patients receiving bevacizumab at 5 and 2.5 mg/kg per week were 7.17 (95% CI, 3.91-13.13) and 4.11 (95% CI 2.49-6.78), respectively. Among cancer patients, those with renal cell carcinoma (RR 13.77, 95% CI 2.28-83.15) and breast cancer (RR 18.83, 95% CI 1.23-292.29) who received bevacizumab at 5 mg/kg per week had a higher risk of developing significantly raised blood pressure.

Conclusions: Among the patients included in the trials analyzed in this meta-analysis, the addition of bevacizumab to cancer therapy treatments significantly increased the risk of significantly raised blood pressure. The risk may be dose-dependent and vary with tumor type.

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Autonomic Nervous System Diseases / chemically induced
  • Autonomic Nervous System Diseases / drug therapy
  • Autonomic Nervous System Diseases / epidemiology*
  • Bevacizumab
  • Breast Neoplasms / chemically induced
  • Breast Neoplasms / drug therapy
  • Carcinoma, Renal Cell / chemically induced
  • Carcinoma, Renal Cell / drug therapy
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / epidemiology*
  • Female
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / epidemiology
  • Hypertension / metabolism
  • Incidence
  • Meta-Analysis as Topic*
  • Neoplasms / chemically induced
  • Neoplasms / drug therapy*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Vascular Endothelial Growth Factor A / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Vascular Endothelial Growth Factor A
  • Bevacizumab