Risk of Dyslipidemia Associated with VEGF/VEGFR Inhibitors: A Meta-Analysis

OBJECTIVE: This meta-analysis was performed to investigate hyperlipidemia in patients with carcinoma treated with vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitors. METHODS: We searched for eligible phase II and III studies using PubMed and Embase databases. We then summarized reported occurrences of hyperlipidemia in patients with different cancers. Relative risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by Revman 5 software in meta-analysis. RESULTS: Eleven trials (4760 subjects) were included in this meta-analysis. Overall, VEGF/VEGFR inhibitors had similar incidence of hypertriglyceridemia (RR = 0.56, 95% CI = 0.24%-1.32%, P = .19), hypercholesterolemia (RR = 1.15, 95% CI = 0.42%-3.16%, P = .78), and LDL elevation (RR = 4.58, 95% CI = 0.80%-26.25%, P = .09) than control drugs, under high heterogeneity. Moreover, subgroup analyses found VEGF/VEGFR inhibitors had higher incidence of hypertriglyceridemia (RR = 1.86, 95% CI = 1.37%-2.52%, P < .001) and hypercholesterolemia (RR = 2.95, 95% CI = 2.02%-4.30%, P = .006) than blank control or placebo control drugs (placebo-controlled-group), although with lower incidence of hypertriglyceridemia (RR = 0.29, 95% CI = 0.12%-0.69%, P < .001) and hypercholesterolemia (RR = 0.39, 95% CI = 0.28%-0.56%, P < .001) than positive control drugs (positive-controlled-groups). CONCLUSION: The use of VEGF/VEGFR inhibitors, especially the multitargeted VEGFR tyrosine kinase inhibitors (VEGFR-TKIs), was associated with higher risk of hyperlipidemia than the use of placebo, but this risk was less than that associated with mTOR or FGFR inhibitors. It indicated that clinicians need to pay close attention to the occurrence of hyperlipidemia in VEGFR-TKIs therapies.