328PD - Effectiveness of antiangiogenic drugs (ADs) in glioblastoma (GBM) patients (PTS): a metanalysis of randomized clinical trials (RCTs)

Abstract

GBMs are highly vascularized tumors and various ADs have been investigated in clinical trials showing unclear results. We performed this metanalysis to evaluate the effectiveness of ADs, in terms of progression-free survival (PFS) and overall survival (OS), as first or second-line therapy and their association with chemotherapy in GBM PTS. The authors searched relevant published and unpublished RCTs analyzing ADs versus chemotherapy in GBM PTS from 2000 to January 2016 in MEDLINE, WEB of SCIENCE, ASCO, ESMO and SNO databases. Sixteen RCTs (9 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) were identified including 4566 PTS. All trials showed no improvement in OS with a pooled HR of 1.02 (95% CI 0.93-1.1; p = 0.7). The use of bevacizumab (BEV) did not improve OS; indeed, the pooled HR for OS for BEV studies (9 studies, 2752 PTS) was 0.98 (95% CI 0.89-1.08; p = 0.7); 6 RCTs (2084 PTS) analyzed BEV as first-line and the pooled HR for OS was 1.02 (95% CI 0.88-1.19; p = 0.8); 3 RCTs studied BEV as second-line therapy and the pooled HR for OS was 0.95 (95% CI 0.77-1.17; p = 0.6). No improvement of OS was shown when BEV was associated with chemotherapy (2588 PTS) with a pooled HR of 0.99 (95% CI 0.88-1.11; p = 0.8). Seven RCTs with a different AD demonstrating no improvement of OS versus standard treatment with a pooled HR of 1.05 (95% CI 0.89-1.23; p = 0.5). 14 RCTs (4349 PTS) were analyzed for PFS and the use of ADs showed a statistically longer PFS with a pooled HR of 0.73 (95% CI 0.62-0.86;p < 0.01); However, among ADs, only bevacizumab (2752 PTS) demonstrated an improvement of PFS; indeed, the pooled HR for PFS for BEV studies was significant at HR = 0.6 (95% CI 0.5-0.7; p < 0.01), both alone (HR = 0.6; CI 95% 0.44-0.82; p < 0.01) or in combination to CT (HR = 0.6; 95% CI 0.4-0.7;p < 0.01), both as first-line treatment (HR = 0.65; 95% CI 0.52-0.83; p < 0.01) or in recurrent disease (HR = 0.51; 95% CI 0.43-0.61; p < 0.01). ADs did not improve OS in GBM PTS, both as first or second-line treatment. Among ADs, only BEV demonstrated a PFS benefit both as single agent or in combination with chemotherapy, both as first or second-line treatment.