A randomized trial of bevacizumab for newly diagnosed glioblastoma

Mark R. Gilbert, James J. Dignam, Terri S. Armstrong, Jeffrey S. Wefel, Deborah T. Blumenthal, Michael A. Vogelbaum, Howard Colman, Arnab Chakravarti, Stephanie Pugh, Minhee Won, Robert Jeraj, Paul D. Brown, Kurt Jaeckle, David Schiff, Volker W. Stieber, David G. Brachman, Maria Werner-Wasik, Ivo W. Tremont-Lukats, Erik P. Sulman, Kenneth D. Aldape & 2 others Walter J. Curran, Minesh P. Mehta

Research output: Contribution to journalArticle

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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.)

Original languageEnglish (US)
Pages (from-to)699-708
Number of pages10
JournalNew England Journal of Medicine
Volume370
Issue number8
DOIs
StatePublished - Jan 1 2014

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Glioblastoma
temozolomide
Radiotherapy
Placebos
Risk Reduction Behavior
Disease-Free Survival
Survival
Bevacizumab
Maintenance Chemotherapy
Intestinal Perforation
Antibodies, Monoclonal, Humanized
National Cancer Institute (U.S.)
Therapeutics
Standard of Care
Random Allocation
Neutropenia
Vascular Endothelial Growth Factor A
Disease Progression
Maintenance
Quality of Life

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Gilbert, M. R., Dignam, J. J., Armstrong, T. S., Wefel, J. S., Blumenthal, D. T., Vogelbaum, M. A., ... Mehta, M. P. (2014). A randomized trial of bevacizumab for newly diagnosed glioblastoma. New England Journal of Medicine, 370(8), 699-708. https://doi.org/10.1056/NEJMoa1308573
Gilbert, Mark R. ; Dignam, James J. ; Armstrong, Terri S. ; Wefel, Jeffrey S. ; Blumenthal, Deborah T. ; Vogelbaum, Michael A. ; Colman, Howard ; Chakravarti, Arnab ; Pugh, Stephanie ; Won, Minhee ; Jeraj, Robert ; Brown, Paul D. ; Jaeckle, Kurt ; Schiff, David ; Stieber, Volker W. ; Brachman, David G. ; Werner-Wasik, Maria ; Tremont-Lukats, Ivo W. ; Sulman, Erik P. ; Aldape, Kenneth D. ; Curran, Walter J. ; Mehta, Minesh P. / A randomized trial of bevacizumab for newly diagnosed glioblastoma. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 8. pp. 699-708.
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Gilbert, MR, Dignam, JJ, Armstrong, TS, Wefel, JS, Blumenthal, DT, Vogelbaum, MA, Colman, H, Chakravarti, A, Pugh, S, Won, M, Jeraj, R, Brown, PD, Jaeckle, K, Schiff, D, Stieber, VW, Brachman, DG, Werner-Wasik, M, Tremont-Lukats, IW, Sulman, EP, Aldape, KD, Curran, WJ & Mehta, MP 2014, 'A randomized trial of bevacizumab for newly diagnosed glioblastoma', New England Journal of Medicine, vol. 370, no. 8, pp. 699-708. https://doi.org/10.1056/NEJMoa1308573

A randomized trial of bevacizumab for newly diagnosed glioblastoma. / Gilbert, Mark R.; Dignam, James J.; Armstrong, Terri S.; Wefel, Jeffrey S.; Blumenthal, Deborah T.; Vogelbaum, Michael A.; Colman, Howard; Chakravarti, Arnab; Pugh, Stephanie; Won, Minhee; Jeraj, Robert; Brown, Paul D.; Jaeckle, Kurt; Schiff, David; Stieber, Volker W.; Brachman, David G.; Werner-Wasik, Maria; Tremont-Lukats, Ivo W.; Sulman, Erik P.; Aldape, Kenneth D.; Curran, Walter J.; Mehta, Minesh P.

In: New England Journal of Medicine, Vol. 370, No. 8, 01.01.2014, p. 699-708.

Research output: Contribution to journalArticle

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T1 - A randomized trial of bevacizumab for newly diagnosed glioblastoma

AU - Gilbert, Mark R.

AU - Dignam, James J.

AU - Armstrong, Terri S.

AU - Wefel, Jeffrey S.

AU - Blumenthal, Deborah T.

AU - Vogelbaum, Michael A.

AU - Colman, Howard

AU - Chakravarti, Arnab

AU - Pugh, Stephanie

AU - Won, Minhee

AU - Jeraj, Robert

AU - Brown, Paul D.

AU - Jaeckle, Kurt

AU - Schiff, David

AU - Stieber, Volker W.

AU - Brachman, David G.

AU - Werner-Wasik, Maria

AU - Tremont-Lukats, Ivo W.

AU - Sulman, Erik P.

AU - Aldape, Kenneth D.

AU - Curran, Walter J.

AU - Mehta, Minesh P.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.)

AB - 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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Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. New England Journal of Medicine. 2014 Jan 1;370(8):699-708. https://doi.org/10.1056/NEJMoa1308573