A randomized trial of bevacizumab for newly diagnosed glioblastoma.
Author(s): Gilbert MR(1), Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA,
Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D,
Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD,
Curran WJ Jr, Mehta MP.
Affiliation(s): Author information:
(1)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.).
Publication date & source: 2014, N Engl J Med. , 370(8):699-708
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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