AbstractBACKGROUNDWe have previously published a Cochrane meta-analysis of the efficacy of anti-angiogenic therapy (AAT) in high grade glioma (HGG) in 2014. Since this time, a number of key trials have been published. An updated meta-analysis was performed to account for these new results.METHODSThe primary analysis was to evaluate the pooled overall survival (OS) of AAT in HGG and the secondary analysis was to evaluate the pooled progression-free survival (PFS) of AAT in HGG. Subgroup analyses were performed according to treatment setting and AAT combined with chemotherapy versus chemotherapy alone. Searches were conducted to identify randomised controlled trials (RCTs) including CENTRAL, MEDLINE and Embase to August 2017. Proceedings of oncology conferences and trial registries were also searched.RESULTS11 eligible RCTs were identified (N=3743). There was no improvement in OS with the addition of AAT (pooled hazard ratio (HR) of 0.95, 95% confidence interval (CI) 0.88, 1.02; p=0.16) overall, or in the adjuvant or recurrent settings (HR 0.93, 95% CI 0.86, 1.02; p=0.12 and HR 0.99, 95% CI 0.85–1.16; p = 0.90). Pooled analysis of OS for AAT with chemotherapy compared to chemotherapy also did not show an improvement (HR 0.92, 95% CI 0.85–1.00; p=0.05). Pooled analysis of PFS from ten studies showed improved PFS with AAT (HR 0.73; 95% CI 0.68, 0.79; p < 0.00001). These improvements in PFS occurred in the adjuvant (HR 0.75, 95% CI 0.69–0.82; p < 0.00001) and recurrent settings (HR 0.64, 95% CI 0.54–0.76; p< 0.00001) and when AAT was combined with chemotherapy compared to chemotherapy alone (HR 0.72, 95% CI 0.66–0.77; p <0.00001). CONCLUSIONS: The use of anti-angiogenic therapy does not improve survival in newly diagnosed people with GBM, despite improved progression free survival. There is no evidence of a survival advantage for anti-angiogenic therapy over chemotherapy in recurrent GBM.