Clinical Drug Investigation

, Volume 34, Issue 4, pp 231–240 | Cite as

Risk of Hypertension in Cancer Patients Treated with Aflibercept: A Systematic Review and Meta-Analysis

Systematic Review



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.


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.


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).


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.



We are indebted to the authors of the primary studies, for without their contributions, this work would have been impossible.

Conflicts of interest

All authors declare that they have no potential conflicts of interests.



Supplementary material

40261_2014_174_MOESM1_ESM.pdf (103 kb)
Supplementary material 1 (PDF 102 kb)


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of OncologyShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina

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