title: A randomized trial of bevacizumab for newly diagnosed glioblastoma.
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.).
authors.affiliation: From the University of Texas M.D. Anderson Cancer Center (M.R.G., T.S.A., J.S.W., P.D.B., I.W.T.-L., E.P.S., K.D.A.) and the University of Texas Health Science Center School of Nursing (T.S.A.), Houston; American College of Radiology (J.J.D., S.P., M.W.) and Thomas Jefferson University (M.W.-W.) - both in Philadelphia; the University of Chicago, Chicago (J.J.D.); Tel-Aviv Medical Center, Tel Aviv, Israel (D.T.B.); Cleveland Clinic, Cleveland (M.A.V.); the University of Utah, Salt Lake City (H.C.); Ohio State University, Columbus (A.C.); University of Wisconsin, Madison (R.J.); Mayo Clinic, Jacksonville, FL (K.A.J.); University of Virginia, Charlottesville (D.S.); Southeast Cancer Control Consortium, Winston-Salem, NC (V.W.S.); Barrow Neurologic Institute, Phoenix, AZ (D.G.B.); Emory University, Atlanta (W.J.C.); and the University of Maryland, Baltimore (M.P.M.).
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.forename: James J
authors.initials: JJ
authors.lastname: Dignam
authors.forename: Terri S
authors.initials: TS
authors.lastname: Armstrong
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Wefel
authors.forename: Deborah T
authors.initials: DT
authors.lastname: Blumenthal
authors.forename: Michael A
authors.initials: MA
authors.lastname: Vogelbaum
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Stephanie
authors.initials: S
authors.lastname: Pugh
authors.forename: Minhee
authors.initials: M
authors.lastname: Won
authors.forename: Robert
authors.initials: R
authors.lastname: Jeraj
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Jaeckle
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Volker W
authors.initials: VW
authors.lastname: Stieber
authors.forename: David G
authors.initials: DG
authors.lastname: Brachman
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.forename: Ivo W
authors.initials: IW
authors.lastname: Tremont-Lukats
authors.forename: Erik P
authors.initials: EP
authors.lastname: Sulman
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Curran
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D016016:Proportional Hazards Models; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide