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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 6/2023

28-01-2023 | Glioblastoma | Research

Using EGFR amplification to stratify recurrent glioblastoma treated with immune checkpoint inhibitors

Authors: Joshua S. Friedman, Tomi Jun, Omid Rashidipour, Kuan-lin Huang, Ethan Ellis, Priyanka Kadaba, Puneet Belani, Kambiz Nael, Nadejda M. Tsankova, Robert Sebra, Adília Hormigo

Published in: Cancer Immunology, Immunotherapy | Issue 6/2023

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Abstract

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.
Appendix
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Metadata
Title
Using EGFR amplification to stratify recurrent glioblastoma treated with immune checkpoint inhibitors
Authors
Joshua S. Friedman
Tomi Jun
Omid Rashidipour
Kuan-lin Huang
Ethan Ellis
Priyanka Kadaba
Puneet Belani
Kambiz Nael
Nadejda M. Tsankova
Robert Sebra
Adília Hormigo
Publication date
28-01-2023
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 6/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-023-03381-y

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