High VEGF-A level at baseline predicts poor treatment effect of bevacizumab-based chemotherapy in metastatic colorectal cancer: a meta-analysis.

INTRODUCTION: Bevacizumab (BEV) improves survival of metastatic colorectal cancer (mCRC) patients, but no specific biomarkers can predict which patients will benefit from bevacizumab (BEV). This meta-analysis aimed to evaluate the predictive significance of plasma/intratumoral vascular endothelial growth factor-A (VEGF-A) at baseline in the effectiveness of BEV-based treatment in mCRC. EVIDENCE ACQUISITION: The PubMed, Medline, and Embase were searched to identify eligible studies. The association of high/low VEGF-A level at baseline with progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were analyzed. Subgroup analysis based on sample and chemotherapy was also conducted. The pooled hazard ratio (HR), risk ratio (RR) and 95% confidence interval (95% CI) were calculated to estimate the effects. EVIDENCE SYNTHESIS: Eleven eligible studies were included. This meta-analysis showed that high VEGF-A level at baseline was associated with poor PFS (HR=1.26, 95% CI [1.12, 1.42], P=0.0001) and OS (HR=1.30, 95% CI [1.15, 1.46], P<0.0001) of mCRC patients following BEV-based chemotherapy compared to low VEGF-A level. Subgroup analysis showed that the pooled results of PFS (blood and tumor tissue subgroup) and OS (blood subgroup) were similar to that of overall analysis. However, there was no significant difference in ORR between high and low VEGF-A level in tumor tissue subgroup (RR=0.95, 95% CI [0.53, 1.71], P=0.87). Moreover, the predictive role of high VEGF-A level at baseline was not impacted by various chemotherapies.
CONCLUSIONS: This meta-analysis indicated that high plasma/intratumoral VEGF-A level at baseline could predict poor treatment effect (depressed PFS and OS) of BEV-based chemotherapy in mCRC, although there was no correlation between intratumoral VEGF-A level and ORR following BEV-based treatment.