Inhibition of the VEGF/VEGFR pathway improves survival in advanced kidney cancer : a systematic review and meta-analysis

Despite the improvement in progression-free survival and response rates, none of the five anti- VEGF/VEGFR agents used for treatment of metastatic renal cell carcinoma (mRCC) reported a significant increase in patients' survival. This analysis aims to investigate their effect on overall survival (OS), performing a meta-analysis of the available studies. MEDLINE/PubMed and the Cochrane Library were searched for randomised phase III trials that compared anti-VEGF/VEGFR agents with controls as upfront treatment for mRCC. The search was restricted to phase III trials, and data extraction was conducted according to the PRISMA statement. Five randomised phase III trials were included for a total of 3,469 patients; among these, 1,801 received anti-VEGF/VEGFR agents and 1,668 were treated with a placebo or interferon-α. In the overall population, the reduction in the risk of death was 13% (HR: 0.87; 95%CI, 0.80 - 0.95; p=0.002). When patients were divided based on use of VEGFR agents or an anti-VEGF monoclonal antibody, the reduction in the risk of death was 13% and 12%, respectively. If only treatmentnaïve patients are considered, we can confirm a significant reduction of 12% (HR=0.88; 95%CI, 0.79 - 0.97; p=0.010) in the risk of death. Our analysis reports a positive improvement of OS with the inhibition of the VEGF/VEGFR pathway in mRCC.