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Persist or resist: Immune checkpoint inhibitors in EGFR-mutated NSCLC

Pengcheng Zhu1,2, Zhitong Li1,2, Yuxiang Sun1,2

  • 1Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Jiangsu Cancer Hospital & Nanjing Medical University Affiliated Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China.

Cancer Science
|December 14, 2024
PubMed

Insights

Immune checkpoint inhibitors (ICIs) show limited benefit as monotherapy for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Further research is needed to identify patient subgroups who may respond to ICIs in EGFR-mutated NSCLC.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improve survival in EGFR-mutated non-small cell lung cancer (NSCLC), but resistance is common.
  • Immune checkpoint inhibitors (ICIs) benefit EGFR-wild type NSCLC, but show limited efficacy in EGFR-mutated NSCLC monotherapy.
  • EGFR-mutated NSCLC exhibits significant heterogeneity in tumor mutational burden (TMB), PD-L1 expression, and immune microenvironment.

Purpose of the Study:

  • To review clinical trials of ICIs or combination therapies in EGFR-mutated NSCLC patients.
  • To discuss factors influencing ICI efficacy in this patient population.
  • To explore mutation subtypes and immune microenvironment characteristics of potential ICI responders.

Main Methods:

  • Systematic review of clinical trials involving ICIs in EGFR-mutated NSCLC.
  • Analysis of factors affecting ICI efficacy, including TMB, PD-L1, and immune microenvironment.
  • Correlation of mutation subtypes and microenvironment with treatment response.

Main Results:

  • ICI monotherapy has not demonstrated significant survival benefits in EGFR-mutated NSCLC.
  • EGFR-mutated NSCLC presents diverse immune profiles, impacting ICI response.
  • Identifying predictive biomarkers for ICI efficacy in EGFR-mutated NSCLC is crucial.

Conclusions:

  • The role of ICIs in EGFR-mutated NSCLC requires further elucidation.
  • Personalized treatment strategies considering tumor heterogeneity are essential.
  • Future research should focus on combination therapies and identifying predictive biomarkers for optimal patient selection.
Keywords:
EGFR tyrosine kinase inhibitor (TKI)epidermal growth factor receptor (EGFR)immune checkpoint inhibitor (ICI)non‐small cell lung cancer (NSCLC)tumor immunology

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