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

Koos E. Hovinga, Heather J. McCrea, Cameron Brennan, Jason Huse, Junting Zheng, Yoshua Esquenazi, Katherine S. Panageas, Viviane Tabar

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)337-345
Number of pages9
JournalJournal of neuro-oncology
Volume142
Issue number2
DOIs
StatePublished - Apr 15 2019
Externally publishedYes

Keywords

  • Bevacizumab
  • Classical
  • EGFR
  • Glioblastoma
  • Mesenchymal
  • Proneural

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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