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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Treatment with immune checkpoint inhibitors after EGFR-TKIs in EGFR-mutated lung cancer

Takashi Ito1, Hiromi Nagashima1, Masachika Akiyama1

  • 1Division of Pulmonary Medicine, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan.

Thoracic Cancer
|December 14, 2021
PubMed
Abstract

Insights

Immune checkpoint inhibitors (ICIs) show improved efficacy in non-small cell lung cancer (NSCLC) patients with the L858R EGFR mutation after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment. This finding suggests L858R-mutated NSCLC patients may benefit from ICI therapy post-EGFR-TKI.

Area of Science:

  • Oncology
  • Cancer Research
  • Immunotherapy

Background:

  • Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard for EGFR-mutated non-small cell lung cancer (NSCLC).
  • Immune checkpoint inhibitors (ICIs) are used for various cancers, but show limited efficacy in EGFR-mutated NSCLC.

Purpose of the Study:

  • To investigate the efficacy of ICIs in EGFR-mutated NSCLC patients previously treated with EGFR-TKIs.
  • To identify patient characteristics associated with positive responses to ICI monotherapy.

Main Methods:

  • Retrospective analysis of 25 EGFR-mutated NSCLC patients receiving ICI monotherapy post-EGFR-TKI.
  • Data collected from December 2015 to March 2020 across three institutions.
  • Responders defined as patients with ≥90 days of ICI treatment.

Main Results:

  • Patients with L858R EGFR mutations showed significantly better response rates to ICIs compared to non-responders (66.7% vs 25.0%, p<0.05).
  • No significant difference in T790M resistance mutation incidence or PD-L1 positivity was observed between responders and non-responders.
  • Patients with L858R mutations had significantly longer survival than those with exon 19 deletions (HR: 0.35, p=0.026).

Conclusions:

  • ICI treatment demonstrates improved efficacy in EGFR-mutated NSCLC patients harboring the L858R mutation.
  • Patients with L858R-mutated NSCLC are potential candidates for ICI therapy following EGFR-TKI treatment.
Keywords:
EGFR mutationEGFR tyrosine kinase inhibitorL858R mutationimmune checkpoint inhibitornon-small cell lung cancer

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