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Onartuzumab Shows No Additional Benefit When Combined With Bevacizumab in GBM

Lisa Miller
Published: Friday, Dec 23, 2016

MGMT methylation, a well-known prognostic marker in glioblastoma, was also explored among 47 patients with methylated MGMT and 57 with unmethylated MGMT. Patients with unmethylated MGMT had better outcomes in the onartuzumab/bevacizumab arm, and multivariate analyses confirmed the potentially predictive effect of treatment with the combination for patients with unmethylated MGMT.

MET status was intended to be a part of the analyses, yet only 5 patients were MET-positive according to a ≥50% staining cutoff by immunohistochemistry, which did not allow for a large enough population to study.

“Although the biomarker data are compelling and should inform future trials targeting the MET pathway, their exploratory nature and relatively small sample size make it difficult to infer firm conclusions on the clinical utility of HGF expression or MGMT methylation as predictive markers in glioblastoma,” the authors said in the study. “Future prospective studies are necessary to validate these results.”


  1. Cloughesy T, Finocchiaro G, Belda-Iniesta C, et al. Randomized, double-blind, placebo-controlled, multicenter phase II study of onartuzumab plus bevacizumab versus placebo plus bevacizumab in patients with recurrent glioblastoma: efficacy, safety, and hepatocyte growth factor and O6-methylguanine–DNA methyltransferase biomarker analyses. [Published online December 5, 2016] J Clin Oncol. doi: 10.1200/JCO.2015.64.7685.
  2. Sandmann T, Bourgon R, Garcia J, et al. Patients with proneural glioblastoma may derive overall survival benefit from the addition of bevacizumab to first-line radiotherapy and temozolomide: Retrospective analysis of the AVAglio trial. J Clin Oncol. 2015;33:2735-2744.

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