As regards safety endpoints, in our pooled analysis anti-VEGF combinations have been shown to significantly increase drug-related risk of bleeding (RR 2.40, 95% CI 1.11–5.23; p = 0.03), arterial hypertension (RR 4.07, 95% CI 1.82–9.09; p = 0.0006), neutropenia (RR 1.34, 95% CI 1.07–1.61; p = 0.002), venous thromboembolism (RR 1.40, 95% CI 1.02–1.92; p = 0.03) and proteinuria (RR 8.48, 95% CI 4.20–17.13; p≤ 0.00001). This evidence concerns the gene VEGFA and Decreased total neutrophil count.