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Published on: November 28, 2015
Using EGFR amplification to stratify recurrent glioblastoma treated with immune checkpoint inhibitors
Joshua S Friedman1, Tomi Jun2, Omid Rashidipour3
1Department of Neurology, Icahn School of Medicine at Mount Sinai, NY, 10029, USA.
Purpose:
While immune checkpoint inhibitors (ICI) have had success with various malignancies, their efficacy in brain cancer is still unclear. Retrospective and prospective studies using PD-1 inhibitors for recurrent glioblastoma (GBM) have not established survival benefit. This study evaluated if ICI may be effective for select patients with recurrent GBM.
Methods:
This was a single-center retrospective study of adult patients diagnosed with first recurrence GBM and received pembrolizumab or nivolumab with or without concurrent bevacizumab. Archival tissue was used for immunohistochemistry (IHC) and targeted DNA next-generation sequencing (NGS) analysis.
Results:
Median overall survival (mOS) from initial diagnosis was 24.5 months (range 10-42). mOS from onset of ICI was 10 months (range 1-31) with 75% surviving > 6 months and 46% > 12 months. Additional IHC analysis on tumors from eight patients demonstrated a trend of longer survival after ICI for those with elevated PD-L1 expression. NGS of samples from 15 patients identified EGFR amplification at initial diagnosis and at any time point to be associated with worse survival after ICI (HR 12.2, 95% CI 1.37-108, p = 0.025 and HR 3.92, 95% CI 1.03-14.9, p = 0.045, respectively). This significance was corroborated with previously tested EGFR amplification via in situ hybridization.
Conclusion:
ICI did not extend overall survival for recurrent GBM. However, molecular sequencing identified EGFR amplification as associated with worse survival. Prospective studies can validate if EGFR amplification is a biomarker of ICI resistance and determine if its use can stratify responders from non-responders.
Insights
Immune checkpoint inhibitors (ICI) did not improve survival in recurrent glioblastoma (GBM). However, EGFR amplification was linked to worse outcomes, suggesting it may predict resistance to ICI therapy.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- Immune checkpoint inhibitors (ICI) show promise in various cancers, but their effectiveness in brain tumors like glioblastoma (GBM) remains uncertain.
- Previous studies on PD-1 inhibitors for recurrent GBM have not demonstrated a clear survival advantage.
Purpose of the Study:
- To evaluate the efficacy of ICI in select patients with recurrent GBM.
- To identify potential biomarkers associated with treatment response or resistance.
Main Methods:
- A single-center retrospective study involving adult patients with first-recurrence GBM treated with pembrolizumab or nivolumab, with or without bevacizumab.
- Immunohistochemistry (IHC) and targeted DNA next-generation sequencing (NGS) were performed on archival tumor tissue.
Main Results:
- Median overall survival from initial diagnosis was 24.5 months; median survival from ICI initiation was 10 months.
- Elevated PD-L1 expression showed a trend towards longer survival post-ICI.
- EGFR amplification, identified via NGS and confirmed by in situ hybridization, was significantly associated with worse survival after ICI treatment.
Conclusions:
- ICI did not extend overall survival in this cohort of recurrent GBM patients.
- EGFR amplification emerged as a potential biomarker for ICI resistance in GBM.
- Further prospective studies are warranted to validate EGFR amplification as a predictive biomarker for stratifying GBM patients for ICI therapy.
