| General information |
| Database: | DB00605 |
| Objective: | Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. |
| Authors: | Gilbert MR, et al |
| Title: | A randomized trial of bevacizumab for newly diagnosed glioblastoma. |
| Journal: | N Engl J Med. |
| Year: | 2014 |
| PMID: | 24552317 |
| Trial Design |
| Clinical Trial Id: | NCT00884741 |
| 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+radiotherapy+maintenance chemotherapy |
| Study Type: | randomized, doubleblind, placebocontrolled trial |
| Key Patients Feature: | patients were eligible for the study if they were at least 18 years of age and had newly diagnosedglioblastoma (World Health Organization [WHO]grade IV astrocytoma), as confirmed on centralreview. Additional eligibility criteria included aKarnofsky performance status of at least 70 (on ascale from 0 to 100, with higher numbers indicating a higher activity level) and adequate hematologic, renal, and hepatic function (Table S1 inthe Supplementary Appendix, available with thefull text of this article at NEJM.org). Patients withactive cardiac disease or recent cerebrovascularevents were excluded. In addition, patients wererequired to undergo an imaging study (computedtomography [CT] or magnetic resonance imaging[MRI]) performed within 1 week before studyregistration) to rule out recent intracranial hemorrhage. Patients who were receiving glucocorticoids had to have received a stable or decreasingdose for the 5 days before study registration.Also required was the submission of a paraffinembedded tumortissue block with a minimumof 1 cm2 of tumor surface area before the initiation of radiotherapy |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | bevacizumab VS placebo |
| Treatment Info: | Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. |
| Primary End Point: | the duration of overall survival from randomization and the duration of progression free survival |
| Secondary End Point: | NA |
| Patients Number: | 978 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79 |
| Median OS A vs. C: | 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13 |
| Adverse Event(agent arm): | There were modest increases in rates of hypertension, thromboembolic events, intestinal perforation, and neutropenia in the bevacizumab group. Over time, an increased symptom burden, a worse quality of life, and a decline in neurocognitive function were more frequent in the bevacizumab group. |
| Conclusions: | Firstline use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. progression free survival was prolonged but did not reach the prespecified improvement target. |