Protracted inhibition of vascular endothelial growth factor signaling improves survival in metastatic colorectal cancer: A systematic review

Clinical data suggest that beyond-progression, the blockade of angiogenesis is associated with improved survivals in colorectal cancer. We conducted a systematic review to investigate the therapeutic effects of antiangiogenic drugs administered as later lines of treatment in patients already progressed to a previous anti-VEGF based treatment. An extensive literature search was conducted. Hazard ratios (HR) for progression (PFS) and death (OS) were extracted. An inverse-variance meta-analysis model was implemented. 6 randomized controlled trials were retrieved, including 3407 patients, treated with different antiangiogenic drugs. All of them had progressed during or after a previous line of treatment with bevacizumab. Overall, both PFS (HR=0.63, P < 0.001) and OS (HR=0.81, P < 0.001) were significantly increased with the use of antiangiogenic drug. No heterogeneity was observed despite different drugs. Protracted inhibition of the VEGF pathway is associated with a significant improvement of both PFS and OS, independently from the antiangiogenic agent used.