Circulating immune response proteins predict the outcome following disease progression of osimertinib treated epidermal growth factor receptor-positive non-small cell lung cancer patients

Christoffer T Maansson, Sofie Helstrup, Eva B F Ebert, Peter Meldgaard, Boe S Sorensen*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

BACKGROUND: Lung cancer patients with sensitizing epidermal growth factor receptor (EGFR) mutations treated with osimertinib will eventually develop progressive disease (PD). The survival following PD varies greatly between patients, and no effective treatment strategy has been established. Furthermore, at the moment, no easily accessible and precise biomarker exists that can predict the survival after PD.

METHODS: We analyzed blood samples drawn from non-small cell lung cancer patients harboring EGFR mutations that were treated with osimertinib. The levels of 92 circulating proteins were analyzed from plasma samples using a proximity extension assay (PEA). The results were evaluated with Gene Ontology (GO) enrichment analysis to reveal patterns of protein expression at progression while on osimertinib treatment.

RESULTS: We found that the expression of 7 proteins were significantly altered at PD, compared to a sample taken at osimertinib response. GO enrichment analysis demonstrated that most of the significant proteins were related to the immune system, specifically the adaptive immune response. Defining two groups of patients, based on the levels of circulating immune response proteins at PD, revealed significant differences in the overall survival (OS) after PD [hazard ratio (HR) =3.04; 95% confidence interval (CI): 1.24-7.45; P=0.0046].

CONCLUSIONS: In this study, we discover novel circulating biomarkers that can predict the OS after PD on osimertinib. These findings support the recent acknowledgement of the immune system's importance in osimertinib resistance.

Original languageEnglish
JournalTranslational Lung Cancer Research
Volume12
Issue1
Pages (from-to)14-26
Number of pages13
ISSN2218-6751
DOIs
Publication statusPublished - Jan 2023

Keywords

  • Osimertinib
  • epidermal growth factor receptor (EGFR)
  • immune response
  • non-small cell lung cancer (NSCLC)
  • resistance

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