Practical prognostic tool for personalising first-line alectinib in ALK-positive NSCLC: A real-world model integrating neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and eosinophil count.

Abstract

e20743 Background: Despite the efficacy of first-line alectinib in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), significant interpatient heterogeneity exists. Robust tools for individualized risk stratification using readily available parameters are lacking. Methods: This retrospective study developed and validated a prognostic nomogram for overall survival (OS). The training cohort comprised 127 patients from a Chinese academic center. The external validation cohort included 64 patients from the US Flatiron Health database. All patients received first-line alectinib. Feature selection was performed using the Boruta algorithm among baseline clinical and laboratory variables. A Cox model was used to build a nomogram, which was assessed by concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: The model identified three independent prognostic factors: neutrophil-to-lymphocyte ratio (NLR), absolute eosinophil count (AEC), and lactate dehydrogenase (LDH). The nomogram demonstrated good discrimination, with a C-index of 0.78 (95% CI: 0.69–0.87) in the training cohort, which was maintained at 0.77 (95% CI: 0.68–0.86) upon external validation. Calibration was excellent across all predicted timepoints (1-5 years). Using an optimal cut-off (57.97 points), patients were stratified into low- and high-risk groups. High-risk patients had significantly inferior median OS (14.7 vs. not reached, P < 0.001) and time to treatment failure (7.7 vs. 62.5 months, P < 0.001) in the training cohort, a finding robustly validated externally. DCA confirmed the clinical utility of the model across a wide range of threshold probabilities. Conclusions: We developed and validated a practical prognostic nomogram based on three routine blood parameters (NLR, AEC, LDH) that effectively stratifies survival in ALK-positive NSCLC patients treated with first-line alectinib. This tool could facilitate personalized risk-adaptive management and enrich future clinical trials.