EGFR amplification and classical subtype are associated with a poor response to bevacizumab in recurrent glioblastoma

Abstract

Purpose 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. Methods 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. Results 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). 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.

Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma

“…It is well established that there are several subtypes of glioblastoma based on their gene expression and DNA mutation characteristics and treatment responses (pro-neural, neural, mesenchymal and classical) 50,51 . EGFR amplification and mutations are more often found in glioblastomas in the classical sub-type 52,53 . Our current results indicate that treatment of TMZ and irradiation selects for a population of cells that have reduced EGFR.…”

CD44 expression in the tumor periphery predicts the responsiveness to bevacizumab in the treatment of recurrent glioblastoma

“…Manneh Kopp et al 21 reported no significant correlation between the clinical outcome in patients with recurrent GBM treated with Bev and histopathological parameters such as the Ki‐67 labeling index, various molecules including c‐Met, HIF‐1, and VEGFA, and neuroradiological parameters. Hovinga et al 22 recently analyzed time to progression in GBM patients treated with Bev and reported that epidermal growth factor receptor amplification and the classical subtype are associated with a poor response to Bev in recurrent GBM. Here, we demonstrated that the P/C ratio of CD44 expression in GBM was significantly correlated with responsiveness to Bev for the treatment of recurrent GBM.…”

Small cell glioblastoma multiforme: a case series and clinicopathological update

“…Bevacizumab has been approved for treatment of recurrent HGG and improves the steroid-free interval and progression-free survival, albeit without an impact on overall survival [ 5 ]. EGFR amplification is associated with poor response to bevacizumab in recurrent GBM [ 6 ]. As most scGBMs show EGFR amplification, the role of bevacizumab is unclear.…”