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Characteristics of Epidermal Growth Factor Receptor-Mutant Nonsmall-Cell Lung Cancer Patients Benefiting From Immune
Haodi Zhou1, Beiyu Liang1, Li-Chin Lu2
1School of Basic Medical Science, Putian University, Putian, China.
Background:
Immune checkpoint inhibitors (ICIs) are used in epidermal growth factor receptor (EGFR)-mutant nonsmall-cell lung cancer (NSCLC) after resistance to targeted therapy; however, responses remain limited. This study identified predictors of ICI efficacy to inform treatment strategies.
Methods:
PubMed, EMBASE, and Web of Science were systematically searched through September 17, 2024, for studies examining associations between clinical benefit and patient characteristics during ICI therapy. Progression-free survival and overall survival were used to determine outcomes.
Results:
We included 18 studies involving 1151 patients. Combination therapy improved outcomes: ICI plus antiangiogenic therapy versus ICI monotherapy (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.36-1.52) and ICI plus chemotherapy versus ICI monotherapy (HR = 0.45, 95% CI: 0.32-0.65). Predictive genetic factors included atypical versus classical EGFR mutations (HR = 0.45, 95% CI: 0.32-0.64) and exon 21 L858R versus exon 19 deletions (HR = 0.53, 95% CI: 0.40-0.71). Favorable biomarkers included low neutrophil-to-lymphocyte ratio (NLR; HR = 1.90, 95% CI: 1.16-3.11) and positive programmed death ligand-1 (PD-L1) expression (HR = 0.58, 95% CI: 0.35-0.96). Poor Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) was associated with poor outcomes (HR = 2.03, 95% CI: 1.37-3.01). Age, sex, smoking status, and histological subtype exhibited weaker or nonsignificant associations.
Conclusion:
Patients with atypical EGFR or L858R mutations, high PD-L1 expression, low NLR, and good ECOG-PS are more likely to benefit from ICI therapy. Combining ICIs with chemotherapy or antiangiogenic agents enhances efficacy. Younger age, smoking history, and squamous cell carcinoma may also associate with improved outcomes, but further validation is required.
Insights
Immune checkpoint inhibitors (ICIs) show limited response in EGFR-mutant NSCLC. Atypical EGFR mutations, low NLR, and PD-L1 expression predict better ICI efficacy, with combination therapies improving outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Genetics
Background:
- Immune checkpoint inhibitors (ICIs) are utilized in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) post-targeted therapy resistance.
- Limited patient responses highlight the need to identify predictors of ICI efficacy.
Purpose of the Study:
- To identify clinical and genetic factors predicting response to ICI therapy in EGFR-mutant NSCLC.
- To evaluate the efficacy of combination therapies (ICI plus chemotherapy or antiangiogenic agents).
Main Methods:
- Systematic literature search of PubMed, EMBASE, and Web of Science up to September 17, 2024.
- Inclusion of 18 studies with 1151 patients analyzing associations between patient characteristics and clinical benefit.
- Progression-free survival and overall survival were primary outcome measures.
Main Results:
- Combination therapy (ICI plus chemotherapy/antiangiogenic) demonstrated improved outcomes compared to ICI monotherapy.
- Predictive genetic factors included atypical EGFR mutations and exon 21 L858R mutations.
- Favorable biomarkers: low neutrophil-to-lymphocyte ratio (NLR) and positive programmed death ligand-1 (PD-L1) expression. Poor Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) correlated with worse outcomes.
Conclusions:
- Patients with atypical EGFR mutations, L858R mutations, high PD-L1, low NLR, and good ECOG-PS are more likely to respond to ICIs.
- Combination therapies enhance ICI efficacy in this patient population.
- Further validation is needed for associations with younger age, smoking history, and squamous cell carcinoma.
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