Onartuzumab does not improve clinical outcomes for patients with glioblastoma when given with bevacizumab, according to a study published in the Journal of Clinical Oncology.1 There is some evidence, however, that high HGF expression or unmethylated MGMT predicts an improved outcome with this treatment combination.
Bevacizumab offers some clinical benefit in glioblastoma, though the cancer invariably develops resistance to the drug. With the hypothesis that the mesenchymal-epithelial transition factor (MET) pathway plays a role in bevacizumab resistance, researchers evaluated whether adding onartuzumab, a monoclonal anti-MET antibody, to bevacizumab would improve clinical outcomes in glioblastoma.
In the phase 2 GO27819 study (ClinicalTrials.gov Identifier: NCT01632228), researchers enrolled 129 patients to receive onartuzumab and bevacizumab (64 patients) or placebo and bevacizumab (65 patients).
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The median progression-free survival was 3.9 months in the onartuzumab arm vs 2.9 months with placebo; the median overall survival, however, was 8.8 months in the onartuzumab arm vs 12.6 with placebo.
The authors noted that high HGF expression and MGMT methylation status were independently predictive of treatment response, though these biomarkers should be investigated further.
Adverse events of any grade occurred among 70.8% of patients in the onartuzumab arm vs 57.8% in the placebo arm. Serious adverse events occurred among about a third of patients in either group.
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The authors concluded that while onartuzumab does not improve clinical outcomes in glioblastoma, HGF expression and MGMT methylation status may be predictive biomarkers for response in this treatment setting.
Reference
- 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. J Clin Oncol. 2016 Dec 15. doi: 10.1200/JCO.2015.64.7685 [Epub ahead of print]
