Risk of hypertension in cancer patients treated with aflibercept: a systematic review and meta-analysis

Clin Drug Investig. 2014 Apr;34(4):231-40. doi: 10.1007/s40261-014-0174-5.


Background: Aflibercept is currently approved as second-line treatment for patients with metastatic colorectal cancer, and its application in other types of tumors is undergoing clinical evaluation. Hypertension is one of its major adverse effects with a substantial variation in the reported incidences and has not been systematically investigated.

Methods: We searched PubMed, EMBASE, and Cochrane Library databases from January 2000 to August 2013 and abstracts presented at annual meetings from 2004 to 2013 to identify relevant studies. Eligible studies were phase II and III prospective clinical trials of aflibercept in patients with any type of cancer describing events of hypertension. Summary incidence rates, odds ratios (OR), and 95 % confidence intervals (CIs) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.

Results: A total of 15 trials with 4,451 patients were included for the meta-analysis. The summary incidences of all-grade and high-grade hypertension were 42.4 % (95 % CI 35.0-50.3) and 17.4 % (95 % CI 13.7-21.9), respectively. The use of aflibercept in cancer patients was associated with a significantly increased risk of all-grade (OR 4.47, 95 % CI 3.84-5.22, p < 0.001) and high-grade (OR 4.97, 95 % CI 3.95-6.27, p < 0.001) hypertension. The risk of developing hypertension with aflibercept was significantly higher than that of bevacizumab (all-grade: OR 1.93, 95 % CI 1.61-2.32, p < 0.001; high-grade: OR 2.06, 95 % CI 1.79-2.37, p < 0.001).

Conclusions: The use of aflibercept is associated with a significantly increased risk of developing all-grade and high-grade hypertension compared with control. Close monitoring and adequate managements are highly recommended to decrease cardiovascular complication.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Agents / adverse effects
  • Bevacizumab
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / complications*
  • Incidence
  • Neoplasms / complications*
  • Neoplasms / drug therapy*
  • Prospective Studies
  • Receptors, Vascular Endothelial Growth Factor / adverse effects*
  • Recombinant Fusion Proteins / adverse effects*
  • Risk Assessment


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Recombinant Fusion Proteins
  • aflibercept
  • Bevacizumab
  • Receptors, Vascular Endothelial Growth Factor