BACKGROUND: glioblastomas are highly vascularized tumors and various 
antiangiogenic drugs have been investigated in clinical trials showing unclear 
results. We performed a systematic review and a meta-analysis to clarify and 
evaluate their effectiveness in glioblastoma patients.
PATIENTS AND METHODS: we searched relevant published and unpublished randomized 
clinical trials analyzing antiangiogenic drugs versus chemotherapy in 
glioblastoma patients from January 2006 to January 2016 in MEDLINE, WEB of 
SCIENCE, ASCO, ESMO and SNO databases.
RESULTS: fourteen randomized clinical trials were identified (7 with 
bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 
temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed 
no improvement in overall survival with a pooled HR of 1.00, a trend for an 
inferior outcome, in terms of overall survival, was observed in the group of 
patients receiving antiangiogenic drug alone compared to cytotoxic drug alone 
(HR=1.24, p=0.056). Bevacizumab did not improve overall survival. Twelve trials 
(4113 patients) were analyzed for progression-free survival. Among 
antiangiogenic drugs, only bevacizumab demonstrated an improvement of 
progression-free survival (HR=0.63, p<0.001), both alone (HR=0.60, p=0.003) or 
in combination to chemotherapy (HR=0.63; p<0.001), both as first-line treatment 
(HR=0.70, p<0.001) or in recurrent disease (HR=0.52, p<0.001).
CONCLUSIONS: antiangiogenic drugs did not improve overall survival in 
glioblastoma patients, either as first or second-line treatment, and either as 
single agent or in combination with chemotherapy. Among antiangiogenic drugs, 
only bevacizumab improved progression-free survival regardless of treatment 
line, both as single agent or in combination with chemotherapy.