Correlation of EGFR, IDH1 and PTEN status with the outcome of patients with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking monoclonal antibody cetuximab

Lv,Shasha; Teugels,Erik; Sadones,Jan; De Brakeleer,Sylvia; Duerinck,Johnny; Du Four,Stephanie; Michotte,Alex; De Grève,Jacques; Neyns,Bart

doi:10.3892/ijo.2012.1539

Correlation of EGFR, IDH1 and PTEN status with the outcome of patients with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking monoclonal antibody cetuximab

Authors:
- Shasha Lv
- Erik Teugels
- Jan Sadones
- Sylvia De Brakeleer
- Johnny Duerinck
- Stephanie Du Four
- Alex Michotte
- Jacques De Grève
- Bart Neyns
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Affiliations: Laboratory of Molecular Oncology and Department of Medical Oncology, University Hospital Brussels, Free University Brussels, 1090 Brussels, Belgium, Department of Pathology, University Hospital Brussels, Free University Brussels, 1090 Brussels, Belgium
Published online on: June 29, 2012 https://doi.org/10.3892/ijo.2012.1539
Pages: 1029-1035

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Abstract

Mutation and gene amplification of the epithelial growth factor receptor (EGFR) is one of the most common genetic alterations in glioblastoma (GB). EGFR is, therefore, an attractive molecular target for the treatment of GB. EGFR-targeted therapies however have been largely ineffective in clinical trials. In this study, we investigated the correlation between the EGFR gene amplification status, expression of the EGFR variant III (EGFRvIII) and EGFR variant IV (EGFRvIV) mutations, expression of the phosphatase and tensin homologue gene on chromosome 10 (PTEN) and mutation of the isocitrate dehydrogenase 1 (IDH1) gene and the survival of patients suffering from recurrent glioblastoma who were treated with the EGFR-targeted monoclonal antibody cetuximab in a prospective phase II clinical trial. EGFR amplification was detected in 19 out of 35 GB (54%), EGFRvIII expression in 11 (31.4%) and EGFRvIV expression in 7 (20%). The EGFRvIII and EGFRvIV mutations were exclusively found in GB with EGFR amplification and were almost mutually exclusive with IDH1 mutation (EGFRvIII mutation was found in 1 out of 11 GB with an IDH1 mutation). Patients with an EGFR amplification lacking EGFRvIII expression had a significantly superior progression free survival (PFS) and a numerical better overall survival (OS) following treatment with cetuximab [median PFS 3.03 vs. 1.63 months (p=0.006); median OS 5.57 vs. 3.97 months (p=0.12)]. Within the subgroup of patients with EGFR amplification, patients with EGFRvIII positive glioblastoma had a worse survival [median PFS 1.63 vs. 3.03 months (p=0.01); median OS 3.27 vs. 5.57 months (p=0.08)]. Our observations indicate that the type of EGFR mutation may determine the outcome of GB patients treated with cetuximab. Prospective investigation of both the EGFR amplification and mutation status in clinical trials with EGFR-targeted therapies for GB is indicated.

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