Abstract
(1)Background: Among new anti-angiogenetic agents being developed and everchanging guidelines indications, the question of benefits/safety ratio remains unclear. (2)Methods: we have conducted a systematic review and meta-analysis of 25 randomized controlled trials (15487 patients), evaluating overall survival – OS, progression free survival– PFS and toxicity (grade ≥3 adverse effects, type and number of all adverse effects. (3)Results: analysis showed improvement of pooled-PFS (HR 0.72, 95%CI 0.66–0.78, I2 = 77%, P<0.00001) regardless of treatment settings (first-line - HR 0.83, 95%CI 0.77-0.90, P<0.00001, recurrent cancer – HR 0.61, 95%CI 0.54-0.68, P<0.00001 or maintenance – HR 0.82, 95%CI 0.67-1.00, P=0.04) and type of anti-angiogenetic drug used (VEGF inhibitors, VEGF-R inhibitors or angiopoietin inhibitors). Improved OS was also observed (HR 0.95, 95%CI 0.91–0.99, P=0.02). OS benefits were only observed in recurrent platinum-sensitive or platinum-resistant cancers. Grade≥3 adverse effects were increased across all trials. Anti-angiogenetic therapy increased the risk of hypertension, infection, thromboembolic/ hemorrhagic events, gastro-intestinal perforations but not the risk of wound related issues, anemia or posterior leukoencephalopathy syndrome. (4)Conclusions: Although angiogenesis inhibitors improve PFS, there is little to no OS benefits. Given the high risk of severe adverse reactions a careful selection of patients is required for obtaining the best results possible.