Predictive value of inflammatory biomarkers in EGFRmutant NSCLC treated with lazertinib: An interim analysis of a prospective real-world study (OREINT)

초록

Background: Systemic inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV) have emerged as potential prognostic biomarkers in various cancers. However, their predictive role in patients receiving third-generation EGFR-TKIs remains uncertain. This study prospectively evaluated the prognostic impact of baseline and early changes in inflammatory biomarkers in EGFR-mutant NSCLC patients treated with lazertinib. Methods: This is a prospective observational study involving 100 patients with EGFR-mutant NSCLC who received lazertinib. Biomarkers including NLR, PLR, SIRI, and PIV were measured at baseline and at first treatment assessment (TA). Patients were stratified into high vs. low groups based on optimal cutoffs, and their associations with progression-free survival (PFS) were analyzed using Cox proportional hazards models. Results: Elevated baseline PIV (≥918.44) was strongly associated with worse PFS (adjusted HR: 4.89, 95% CI: 2.19–10.92, p < 0.001), as were high baseline PLR (HR: 5.93, 95% CI: 2.51–14.04, p < 0.001), NLR (HR: 2.94, 95% CI: 1.23–7.01, p = 0.015), and SIRI (HR: 2.96, 95% CI: 1.11–7.89, p = 0.030). Dynamic changes in biomarkers also held predictive value: a ≥84.1% increase in NLR was associated with a markedly worse PFS (adjusted HR: 17.63, 95% CI: 5.30–58.69, p < 0.001). Similar findings were observed for increases in PLR (adjusted HR: 10.40, 95% CI: 2.90–37.26, p < 0.001). In contrast, patients with low baseline biomarker levels and minimal increases over time showed favorable outcomes with lazertinib. This trend was consistent regardless of lines of therapy. Conclusions: Inflammatory biomarkers at baseline and their early changes during treatment may serve as potent predictive indicators of treatment outcomes in patients with EGFR-mutant NSCLC receiving lazertinib. PIV and NLR in particular demonstrated strong prognostic power. Incorporating these biomarkers into clinical decision-making could improve risk stratification and guide therapy optimization.