Two Phase III trials do not show improved GBM survival with addition of bevacizumab
The New England Journal of Medicine (Feb ‘14) reported results from two randomized, double-blind, placebo-controlled Phase III trials testing addition of bevacizumab (BEV) to standard radiation + temozolomide therapy for newly-diagnosed glioblastoma (GBM): Radiation Therapy Oncology Group 0825 and ‘Avastin in glioblastoma’ (AVAglio).
RTOG 0825 randomized GBM patients to BEV vs. placebo during week 4 of radiation therapy and up to 12 cycles of maintenance chemotherapy. It was powered to detect 25% mortality risk reduction, and 30% risk reduction in progression or death. No significant difference in median survival was observed between the BEV (n=320) vs. placebo (n=317) groups (15.7 vs. 16.1 months). BEV was associated with improved PFS (10.7 vs. 7.3 months), but with increased rates of hypertension, thromboembolic events, and neutropenia.
AVAglio trial randomized GBM patients to standard therapy + BEV vs. placebo for 6 weeks. After a 4-week treatment break, temozolomide + maintenance BEV vs. placebo was continued for six cycles. BEV-treated patients (n=458) vs. placebo (n=463) showed overall survival of 72.4% vs. 66.3% at 1 year (p = 0.049) and 33.9% vs. 30.1% at 2 years (p = 0.24). BEV (10.6 vs. 6.2 months) was also associated with improved PFS.
Interestingly, baseline health-related quality of life and performance status were maintained longer with BEV and lower steroid requirements in AVAglio; whereas RTOG0825 showed worse neurocognitive performance with BEV, and observed more severe BEV-associated adverse events (32.5% vs. 15.8%). Both studies showed that addition of BEV did not improve standard therapy for newly-diagnosed GBM.