Lomustine and bevacizumab in progressive glioblastoma

Wolfgang Wick*, Thierry Gorlia, Martin Bendszus, Martin Taphoorn, Felix Sahm, Inga Harting, Alba A. Brandes, Walter Taal, Julien Domont, Ahmed Idbaih, Mario Campone, Paul M. Clement, Roger Stupp, Michel Fabbro, Emilie Le Rhun, Francois Dubois, Michael Weller, Andreas Von Deimling, Vassilis Golfinopoulos, Jacoline C. BrombergMichael Platten, Martin Klein, Martin J. Van Den Bent

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma. METHODS: We randomly assigned patients with progression after chemoradiation in a 2:1 ratio to receive lomustine plus bevacizumab (combination group, 288 patients) or lomustine alone (monotherapy group, 149 patients). The methylation status of the promoter of O6methylguanine–DNA methyltransferase (MGMT) was assessed. Healthrelated quality of life and neurocognitive function were evaluated at baseline and every 12 weeks. The primary end point of the trial was overall survival. RESULTS: A total of 437 patients underwent randomization. The median number of 6week treatment cycles was three in the combination group and one in the monotherapy group. With 329 overall survival events (75.3%), the combination therapy did not provide a survival advantage; the median overall survival was 9.1 months (95% confidence interval [CI], 8.1 to 10.1) in the combination group and 8.6 months (95% CI, 7.6 to 10.4) in the monotherapy group (hazard ratio for death, 0.95; 95% CI, 0.74 to 1.21; P=0.65). Locally assessed progression-free survival was 2.7 months longer in the combination group than in the monotherapy group: 4.2 months versus 1.5 months (hazard ratio for disease progression or death, 0.49; 95% CI, 0.39 to 0.61; P<0.001). Grade 3 to 5 adverse events occurred in 63.6% of the patients in the combination group and 38.1% of the patients in the monotherapy group. The addition of bevacizumab to lomustine affected neither healthrelated quality of life nor neurocognitive function. The MGMT status was prognostic. CONCLUSIONS: Despite somewhat prolonged progressionfree survival, treatment with lomustine plus bevacizumab did not confer a survival advantage over treatment with lomustine alone in patients with progressive glioblastoma. (Funded by an unrestricted educational grant from F. Hoffmann–La Roche and by the EORTC Cancer Research Fund; EORTC 26101 ClinicalTrials.gov number, NCT01290939; EudraCT number, 201002321830.)

Original languageEnglish
Pages (from-to)1954-1963
Number of pages10
JournalNew England Journal of Medicine
Volume377
Issue number20
DOIs
Publication statusPublished - 16 Nov 2017

Cite this

Wick, W., Gorlia, T., Bendszus, M., Taphoorn, M., Sahm, F., Harting, I., ... Van Den Bent, M. J. (2017). Lomustine and bevacizumab in progressive glioblastoma. New England Journal of Medicine, 377(20), 1954-1963. https://doi.org/10.1056/NEJMoa1707358