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Published on: September 8, 2023
Hope and Challenges: Immunotherapy in EGFR-Mutant NSCLC Patients
Dan Yan1,2
1Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Abstract:
EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. Sadly, remission is transient, and no approved effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Although immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs, ICI therapy exhibits limited activity in most EGFR-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in EGFR-mutant NSCLCs contributes to a non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8+ T cell infiltration, a high number of regulatory CD4+ T cells, and an increased number of inactivated infiltrated T cells. Additionally, EGFR-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. Promisingly, a small population of EGFR-mutant NSCLCs still durably respond to ICI therapy. The hope of ICI therapy from pre-clinical studies and clinical trials is reviewed in EGFR-mutant NSCLCs. The challenges of application ICI therapy in EGFR-mutant NSCLCs are also reviewed.
Insights
EGFR tyrosine kinase inhibitors (TKIs) offer initial non-small cell lung cancer (NSCLC) treatment, but resistance emerges. Immunotherapy shows limited efficacy in EGFR-mutant NSCLC due to a non-inflamed tumor microenvironment.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- EGFR tyrosine kinase inhibitors (TKIs) are first-line treatments for EGFR-mutant non-small cell lung cancer (NSCLC).
- Tumor resistance to EGFR TKIs is common, with limited subsequent treatment options.
- Immune checkpoint inhibitors (ICIs) show potential but have low efficacy in most EGFR-mutant NSCLC.
Purpose of the Study:
- To review the potential of ICI therapy in EGFR-mutant NSCLC.
- To discuss the challenges and limitations of ICI therapy in this patient population.
Main Methods:
- Review of pre-clinical studies.
- Analysis of clinical trial data.
- Examination of the tumor immune microenvironment (TIME) in EGFR-mutant NSCLC.
Main Results:
- EGFR signaling creates a non-inflamed TIME, hindering T-cell infiltration and activity.
- EGFR-mutant NSCLC often presents with low PD-L1 expression and tumor mutational burden.
- A subset of patients with EGFR-mutant NSCLC shows durable responses to ICIs.
Conclusions:
- Despite challenges, ICI therapy holds promise for a subset of EGFR-mutant NSCLC patients.
- Understanding the TIME is crucial for improving ICI efficacy in EGFR-mutant NSCLC.
- Further research is needed to overcome resistance mechanisms and optimize ICI treatment strategies.
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