Authors

Mark R Gilbert, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center
James J Dignam, American College of Radiology, Philadelphia; University of Chicago
Terri S Armstrong, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center; University of Texas Health Science Center School of Nursing
Jeffrey S Wefel, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center
Deborah T Blumenthal, Tel-Aviv Medical Center
Michael A Vogelbaum, Cleveland Clinic
Howard Colman, University of Utah, Salt Lake City
Arnab Chakravarti, Ohio State University
Stephanie Pugh, American College of Radiology, Philadelphia
Minhee Won, American College of Radiology, Philadelphia
Robert Jeraj, University of Wisconsin, Madison
Paul D Brown, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center
Kurt A Jaeckle, Mayo Clinic, Jacksonville, FL
David Schiff, University of Virginia, Charlottesville
Volker W Stieber, Southeast Cancer Control Consortium, Winston-Salem, NC
David G Brachman, Barrow Neurologic Institute, Phoenix, AZ,
Maria Werner-Wasik, Thomas Jefferson UniversityFollow
Ivo W Tremont-Lukats, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center
Erik P Sulman, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center
Kenneth D Aldape, Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center
Walter J Curran, Emory University, Atlanta, GA
Minesh P Mehta, University of Maryland, Baltimore

Document Type

Article

Publication Date

2-20-2014

Comments

This article has been peer reviewed. It is the author’s final published version in New England Journal of Medicine Volume 370, Issue 8, February 2014, Pages 699-708.

The published version is available at DOI: 10.1056/NEJMoa1308573. Copyright © Massachusetts Medical Society

Abstract

BACKGROUND: 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.

METHODS: In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. 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. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary end points, with the addition of bevacizumab.

RESULTS: A total of 978 patients were registered, and 637 underwent randomization. There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group (median, 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13). Progression-free survival was longer in the bevacizumab group (10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79). 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: First-line 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. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00884741.).

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