Abstract

Because patients younger than 40years are rarely enrolled in clinical trials in non-small cell lung cancer (NSCLC), their survival benefit of immune checkpoint inhibitors (ICIs) needs to be clarified. The National Cancer Database was queried for patients who were diagnosed with stage IV NSCLC between 2016 and 2018. ICIs were administered in the first-line setting. The overall survival (OS) of patients with stage IV NSCLC according to the receipt of ICIs was compared in different age groups (< 40, 40-49, 50-59, 60-69, 70-79, and ≥ 80years). Multivariate analyses identified the clinical characteristics predictive of OS. Propensity score matching (PSM) was conducted to reduce the biases arising from clinical characteristics. This study included 126,476 patients with stage IV NSCLC. In univariate analysis, ICI treatment was not associated with a survival benefit in patients younger than 40years with stage IV NSCLC relative to their ICI-naïve counterparts after PSM (median OS: 24.2months vs. 24.0months, hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 0.81-1.27,P = 0.9031). Multivariate analysis revealed that ICI use was not an independent predictor of OS in patients with stage IV NSCLC < 40years old (HR = 0.96, 95% CI = 0.76-1.21,P = 0.7230). Sequential improvement of the HR was observed with increasing age. Our study suggested a poor survival benefit of ICIs in stage IV NSCLC patients younger than 40years old, which should be validated in prospective studies.

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