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N Engl J Med. 2014 Feb 20;370(8):709-22. doi: 10.1056/NEJMoa1308345.

Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma.

Author information

1
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.).

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.).

PMID:
24552318
DOI:
10.1056/NEJMoa1308345
[Indexed for MEDLINE]
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