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Tumor Microenvironment Modulation by Neoadjuvant Erlotinib Therapy and Its Clinical Impact on Operable EGFR-Mutant

Beung-Chul Ahn1, Charny Park2, Moon Soo Kim3

  • 1Center for Lung Cancer, Division of Hematology and Oncology, Department of Internal Medicine, Research Institute and Hospital, National Cancer Center, Goyang, Korea.

Cancer Research and Treatment
|June 21, 2023
PubMed
Abstract

Insights

Neoadjuvant erlotinib therapy (NE) impacts the tumor microenvironment (TME) in EGFR-mutant non-small cell lung cancer (NSCLC). Immune pathway activation correlates with better response and survival in NSCLC patients treated with NE.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have improved survival in EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC).
  • The impact of neoadjuvant erlotinib therapy (NE) on the tumor microenvironment (TME) in operable EGFRm NSCLC remains largely unknown.
  • Understanding TME modulation by NE is crucial for optimizing treatment strategies.

Purpose of the Study:

  • To assess the changes induced by neoadjuvant erlotinib therapy (NE) in the tumor microenvironment (TME) of operable EGFR-mutant non-small cell lung cancer (NSCLC).
  • To investigate the correlation between baseline TME characteristics and treatment response to NE.

Main Methods:

  • A single-arm phase II trial involving patients with stage II/IIIA EGFRm NSCLC receiving up to 2 cycles of NE.
  • TME changes were evaluated using gene expression analysis and mutation profiling on resected tumor tissues.
  • Patients received adjuvant therapy based on NE response.

Main Results:

  • The objective response rate to NE was 72% among 25 patients.
  • Gene set enrichment analysis revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways post-NE.
  • Baseline upregulation of pathogen defense, interleukins, and T-cell function pathways was associated with partial response and longer overall survival (OS).
  • Upregulation of cell cycle pathways at baseline correlated with stable/progressive disease and shorter OS.

Conclusions:

  • Neoadjuvant erlotinib therapy (NE) effectively modulates the tumor microenvironment (TME) in EGFR-mutant non-small cell lung cancer (NSCLC).
  • Upregulation of immune-related pathways within the TME is linked to improved clinical outcomes, including response and survival.
  • Baseline immune status influences patient response to NE, suggesting potential for predictive biomarkers.
Keywords:
Epidermal growth factor receptorNeoadjuvant therapyNon-small-cell lung carcinoma

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