308 EGFR Gene Amplification Predicts a Poor Response to Bevacizumab in Recurrent Glioblastoma

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Abstract INTRODUCTION The highly vascular malignant brain tumor glioblastoma multiforme (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 without any benefit on overall survival. Here we analyze a group of patients with GBM who received bevacizumab treatment and are stratified according to tumor molecular and genomic profile (TCGA classification), with the goal of identifying molecular predictors of the response to bevacizumab. METHODS We performed a retrospective review of patients with a diagnosis of glioblastoma multiforme who were treated with bevacizumab in the recurrent setting at Memorial Sloan-Kettering Cancer Center, from 2006 to 2014. Treatment was discontinued by individual neuro-oncologists, based on clinical and radiographic criteria. Pre- and post- treatment imaging and genomic subtype were available on 83 patients; We analyzed clinical progression, and time to radiographic progression (rP) on MRI flair and T1 weighted images with contrast, quantified tumor volumes as well as the development of multifocal lesions. EGFR gene amplification and MGMT promotor methylation status were determined by FISH. RESULTS >EGFR gene amplification was significantly associated with a shorter time to progression both in univariate (P = < 0.001) and multivariate analysis (P = 0.011). Patients with classical tumors had a significantly shorter time to progression than mesenchymal and proneural patients (2.5 vs 6.32 and 5.2 months respectively, P = 0.001), although it lost its significance (P = 0.262) on multivariate analysis when correcting for EGFR status. Overall survival was significantly shorter in patients with EGFR- amplified GBM treated with bevacizumab. CONCLUSION 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.