Characteristics of Epidermal Growth Factor Receptor-Mutant Nonsmall-Cell Lung Cancer Patients Benefiting From Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

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.