Efficacy And Safety Of Addition Of VEGFR-TKIs To Cytotoxic Chemotherapy In (?)etastatic Breast Cancer:a Meta-analysis

Packground and Purposes:The addition of vascular endothelial growth factor receptor tyrosine inase inhibitors (VEGFR-TKIs) to cytotoxic chemotherapy has been explored in several phases Ⅰ/Ⅲ randomized controlled trials (RCTs) for metastatic breast cancer (MBC) patients. However, the dvantages from this combination therapy over chemotherapy alone remain largely unknown. We ndertook a meta-analysis of these studies to evaluate the efficacy and safety of addition of EGFR-TKIs to chemotherapy in metastatic breast cancer.Methods:PubMed, Web of Knowledge databases and the ASCO meeting abstracts were searched or eligible literature published up to August 30,2013. We searched these electronic databases using le combination of "breast cancer" with the following keywords:"sorafenib", "sunitinib", vandetanib", "pazopanib", "axitinib", "cediranib", "BIBF1120", "regorafenib" and "brivanib", espectively. The study endpoints included progression-free survival (PFS), overall survival (OS), verall response rate (ORR) and toxicities. Pooled hazard ratios (HRs) for time to event data survival data) and odds ratio (ORs) for dichotomous data with 95% confidence intervals (CIs) were erived. Pooled estimates were computed using random-effect modeling. This meta-analysis was erformed using the Comprehensive Meta-Analysis software, version 2 (Biostat, Englewood, NJ, USA) and Stata software (version 12.0; StataCorp, College Station, TX) programs.Results:Eight studies including 2,077 participants were analyzed (VEGFR-TKIs containing group: 070 participants, VEGFR-TKIs free group:1007 participants). Compared to chemotherapy alone, dding VEGFR-TKIs to chemotherapy resulted in a 14% risk reduction of PFS events. However, the enefit did not reach statistical significance (HR 0.86; 95% CI 0.70-1.04, P= 0.126). Also, we did ot observe OS benefit (HR 1.03; 95% CI 0.89-1.18, P= 0.724) from the use of VEGFR-TKIs. The addition of VEGFR-TKIs significantly increased the ORR (OR 1.57; 95% CI 1.30-1.91, P= .000). Toxicities were more frequent in patients receiving therapy of VEGFR-TKIs.Conclusion:Overall, regimens consisting of VEGFR-TKIs seemed not to be superior to hemotherapy alone in terms of PFS and OS, although significant improvement in ORR was bserved. Furthermore, VEGFR-TKIs combined to chemotherapy increased the risk of toxicities. urther studies are needed to corroborate this finding.