| General information |
| Database: | DB00604 |
| Objective: | Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In thisphase 3 study, they evaluated the effect of the addition of bevacizumab to radiotherapytemozolomide for the treatment of newly diagnosed glioblastoma. |
| Authors: | Chinot OL, et al |
| Title: | Bevacizumab plus radiotherapytemozolomide for newly diagnosed glioblastoma. |
| Journal: | N Engl J Med. |
| Year: | 2014 |
| PMID: | 24552318 |
| Trial Design |
| Clinical Trial Id: | NCT00943826 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Bevacizumab plus radiotherapytemozolomide |
| Study Type: | phase III a randomized, doubleblind, placebocontrolled trial |
| Key Patients Feature: | Patients 18 years of age or older with newly diagnosed, histologically confirmed, supratentorialglioblastoma were eligible for participation inthe study. Additional inclusion criteria were aWorld Health Organization (WHO) performancestatus of 2 or lotheyr (on a scale of 0 to 5, withhigher numbers indicating decreasing performance); the use of stable or decreasing glucocorticoid doses within the 5 days before randomization;adequate healing of craniotomy or cranialbiopsysite; adequate hematologic, hepatic, and renalfunction; and acceptable blood coagulation levels.Investigators submitted available tumor tissueblocks for pathological central review and analysis of status with respect to O6methylguanine-DNA methyltransferase (MGMT). Treatment hadto be initiated between 29 and 48 days after themost recent surgery. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | bevacizumab VS placebo |
| Treatment Info: | They randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of bodysurface area per day) for 6 weeks. After a 28day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. |
| Primary End Point: | investigatorassessed progression free survival and overall survival |
| Secondary End Point: | NA |
| Patients Number: | 458 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median progression free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). |
| Median OS A vs. C: | 16.8 months in the bevacizumab group and 16.7 months in the placebo group (stratified hazard ratio for death with bevacizumab, 0.88; 95% CI, 0.76 to 1.02; P=0.10) |
| Adverse Event(agent arm): | More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%). |
| Conclusions: | The addition of bevacizumab to radiotherapytemozolomide did not improve survival in patients with glioblastoma. Improved progression free survival and maintenance of baseline quality of life and performance status they were observed with bevacizumab; hotheyver, the rate of adverse events was higher with bevacizumab than with placebo |