title: Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma.
abstract: BACKGROUND
  Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma.
  
  
  METHODS
  We 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 body-surface area per day) for 6 weeks. After a 28-day 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 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival.
  
  
  RESULTS
  A total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. 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). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P=0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P=0.049) and 33.9% and 30.1% at 2 years (P=0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. 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 radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT00943826.).
authors.affiliation: From Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Service de Neuro-Oncologie, Centre Hospitaliere Universitaire Timone, Marseille (O.L.C.), UFR de Santé, Médecine et Biologie Humaine, Bobigny (A.F.C.), and Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de Neurologie, Université Paris 13 (A.F.C.), and AP-HP, Université Pierre-et-Marie-Curie, Group Hospitalier Pitié-Salpêtrière (K.H.-X.), Paris - all in France; University Hospital of Heidelberg, Department of Neurooncology, and German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany (W.W.); Princess Margaret Hospital, Toronto (W.M.), and McGill University, Montreal (P.K.) - both in Canada; Regional Cancer Center, Stockholm Gotland, Karolinska, Stockholm, and the Department of Radiation Sciences and Oncology, Umeå University, Umeå - both in Sweden (R.H.); the Royal Marsden National Health Service Foundation Trust, Sutton, Surrey, United Kingdom (F.S.); Saitama Medical University, Saitama, Japan (R.N.); Oncology Institute "Ion Chiricuta," Cluj-Napoca, Romania (D.C.); Medical Oncology Department, Azienda Unità Sanitaria Locale, Bologna, Italy (A.A.B.); F. Hoffmann-La Roche, Basel, Switzerland (M.H., L.A.); and University of California, Los Angeles, Los Angeles (T.C.).
authors.forename: Olivier L
authors.initials: OL
authors.lastname: Chinot
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Warren
authors.initials: W
authors.lastname: Mason
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.forename: Frank
authors.initials: F
authors.lastname: Saran
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishikawa
authors.forename: Antoine F
authors.initials: AF
authors.lastname: Carpentier
authors.forename: Khe
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: Petr
authors.initials: P
authors.lastname: Kavan
authors.forename: Dana
authors.initials: D
authors.lastname: Cernea
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.forename: Magalie
authors.initials: M
authors.lastname: Hilton
authors.forename: Lauren
authors.initials: L
authors.lastname: Abrey
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; 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; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide