EGFR amplification and classical subtype are associated with a poor response to bevacizumab in recurrent glioblastoma
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The highly vascular malignant brain tumor glioblastoma (GBM) appears to be an ideal target for anti-angiogenic therapy; however, clinical trials to date suggest the VEGF antibody bevacizumab affects only progression-free survival. Here we analyze a group of patients with GBM who received bevacizumab treatment at recurrence and are stratified according to tumor molecular and genomic profile (TCGA classification), with the goal of identifying molecular predictors of the response to bevacizumab.
We performed a retrospective review of patients with a diagnosis of glioblastoma who were treated with bevacizumab in the recurrent setting at our hospital, from 2006 to 2014. Treatment was discontinued by the treating neuro-oncologists, based on clinical and radiographic criteria. Pre- and post-treatment imaging and genomic subtype were available on 80 patients. We analyzed time on bevacizumab and time to progression. EGFR gene amplification was determined by FISH.
Patients with classical tumors had a significantly shorter time on bevacizumab than mesenchymal, and proneural patients (2.7 vs. 5.1 vs. 6.4 and 6.0 months respectively, p = 0.011). Classical subtype and EGFR gene amplification were significantly associated with a shorter time to progression both in univariate (p < 0.001 and p = 0.007, respectively) and multivariate analysis (both p = 0.010).
EGFR gene amplification and classical subtype by TCGA analysis are associated with significantly shorter time to progression for patients with recurrent GBM when treated with bevacizumab. These findings can have a significant impact on decision-making and should be further validated prospectively.
KeywordsBevacizumab Classical EGFR Glioblastoma Mesenchymal Proneural
Compliance with ethical standards
Conflict of interest
All the authors declare that there is no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
The research protocol was submitted to the institutional research board and deemed exempt. No patient consent was required.
- 17.Verhaak RGW, Hoadley KA, Purdom E et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17(1):98–110. https://doi.org/10.1016/j.ccr.2009.12.020 CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Erdem-Eraslan L, van den Bent MJ, Hoogstrate Y et al (2016) Identification of patients with recurrent glioblastoma who may benefit from combined bevacizumab and CCNU therapy: a report from the BELOB trial. Cancer Res 76(3):525–534. https://doi.org/10.1158/0008-5472.CAN-15-0776 CrossRefPubMedGoogle Scholar
- 29.Sandmann T, Bourgon R, Garcia J et al (2015) 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 33(25):2735–2744. https://doi.org/10.1200/JCO.2015.61.5005 CrossRefPubMedPubMedCentralGoogle Scholar