Thromboembolic Events Associated with Bevacizumab plus Chemotherapy for Patients with Colorectal Cancer: A Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Bevacizumab is a recombinant, humanized monoclonal antibody that hinders the proliferation of new blood vessels required for malignant progression. The drug is considered safe and tolerable; however, some controversy remains about whether it is linked to venous and arterial thromboembolic events (TEEs).


OBJECTIVE
To evaluate the risk for overall, venous, and arterial TEEs in patients with colorectal cancer (CRC) who are administered bevacizumab plus chemotherapy in randomized controlled trials (RCTs).


METHODS
We searched PubMed and CENTRAL databases to extract reports of relevant trials that were published in English between January 1, 2003, and December 31, 2014. All RCTs in which bevacizumab plus chemotherapy was compared with standard chemotherapy or with placebo plus chemotherapy for the treatment of CRC, and TEEs were reported, were included in a meta-analysis. Risk ratios (RRs) with 95% confidence intervals (CIs) of TEEs were calculated for each RCT. Because the between-study heterogeneities (I2) were insignificant, a fixed-effect model was used to determine the effect size of each TEE. A funnel plot was created to assess publication bias, and 2 forms of sensitivity analyses were performed for each outcome.


RESULTS
This meta-analysis included 22 RCTs with a total of 13,185 patients. Overall, compared with the control groups, patients with CRC who received bevacizumab were at significant risk for overall TEEs (RR, 1.334; 95% CI, 1.191-1.494; P <.001; I2 = 1.37%). Regarding venous TEEs, a significant risk was observed for patients who received bevacizumab versus control patients (RR, 1.244; 95% CI, 1.091-1.415; P = .001; I2 = 0.0%). Similarly, the risk for arterial TEEs was significant in bevacizumab-treated patients (RR, 1.627; 95% CI, 1.162-2.279; P = .005; I2 = 0.0%). Sensitivity analyses did not affect the level of significance of the effect size for each outcome, and no significant publication bias was observed.


CONCLUSIONS
In all the studies reviewed in this meta-analysis, the risk for venous or arterial TEEs was associated with bevacizumab use in patients with CRC. Healthcare providers are encouraged to consider thromboprophylaxis agents, periodically monitor their patients who receive bevacizumab, and carefully manage patients who are at increased risk for those complications.
Graduate student, University of Cincinnati, College of Pharmacy, OH.
Abdullah K
AK
Alahmari
Graduate student, University of Cincinnati, College of Pharmacy, OH.
Ziyad S
ZS
Almalki
Student, King Khalid University, College of Medicine, Abha, Kingdom of Saudi Arabia.
Ahmed K
AK
Alahmari
Professor, Pharmacoepidemiology & Pharmacoeconomics, College of Pharmacy, University of Cincinnati Academic Health Center, OH.
Jeff J
JJ
Guo
TEEs; arterial thromboembolic events; bevacizumab; colorectal cancer; meta-analysis; randomized controlled trials; venous thromboembolic events
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