Abstract
Immune checkpoint inhibitors (ICIs) combined with chemotherapy (Chemo+ICI) have shown variable benefit in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) whose disease progressed following tyrosine kinase inhibitors (TKIs) therapy. This retrospective study evaluated treatment outcomes between Chemo+ICI and chemotherapy alone, and developed a lymphocyte subset model (LSM) using pre-treatment blood samples to predict survival outcome. Patients receiving Chemo+ICI showed significantly improved overall response rates (34.2% vs. 22.0%, p = 0.04), progression-free survival (6.0 vs. 4.0 months, p < 0.0001), and overall survival (14.6 vs. 11.0 months, p < 0.001). LSM yielded an area under the curve of 0.726, with 58.6% sensitivity and 83.8% specificity. Across training and validation cohorts, patients classified as LSM-high had significantly longer progression-free survival than those in the LSM-low group. These findings provide real-world clinical evidence supporting the benefit of Chemo+ICI in EGFR-TKI-resistant EGFR-mutant NSCLC, and suggest that LSM may help identify patients most likely to benefit from Chemo+ICI.