Disparities in Non-Small Cell Lung Cancer (NSCLC) by Age, Sex, and Race: A Systematic Review and Meta-Analysis of Immune Checkpoint Inhibitor (ICI) Trials

<b>Background:</b> While immune checkpoint inhibitors (ICIs) have improved survival in mNSCLC, outcomes may be disparate by age, race, and sex. However, given the limited diversity of trial populations, data are limited. <b>Methods:</b> A systematic review and meta-analysis were conducted of phase III prospective trials of ICIs in mNSCLC initiated after 2015, identified from PubMed and ClinicalTrials.gov in September 2025. Trials that did not report overall survival by race, sex, or age distribution were excluded. Random-effects meta-analyses were used to pool ratios of hazard ratios (RHRs) for overall survival to assess treatment-by-subgroup interactions by sex (men vs. women), race (white vs. Asian), and age (<65 vs. ≥65). Random-effects meta-analyses of odds ratios (ORs) for death were also performed for each subgroup in the investigational treatment arm and across all patients. Heterogeneity across trials was evaluated by Cochran's Q test and I² statistics. Publication bias was assessed by Egger's tests and funnel plots. <b>Results:</b> A total of 21 trials comprising 10,950 patients were included in the meta-analysis. Women have a non-significantly smaller overall survival benefit with the investigational treatment than with control compared with men (RHR 0.91; <i>p</i> = 0.17). On investigational agents, white patients had higher odds of death (OR 1.76; <i>p</i> = 0.0496) compared to Asian patients. Similarly, white patients had higher odds of death across both treatment arms compared to Asian patients (OR 2.35; <i>p</i> < 0.001). No trials reported subgroup analysis for Black patients due to small sample sizes. Patients ≥65 years old have a non-significantly smaller overall survival benefit with investigational agents compared with control (RHR 0.92; <i>p</i> = 0.19). <b>Discussion:</b> This study did not identify significant differences in overall survival benefit on the investigational treatment across race, sex, or age subgroups. Still, it remains unclear whether women and patients ≥65 years old derive less survival benefit from ICIs than men and younger patients. Asian patients had significantly greater survival than white patients on investigational therapies and all therapies, while Black patients were underrepresented in trials. Our results highlight the need for more representative trial populations and standardized reporting of subgroup analysis to ensure equitable benefit and evaluation of ICIs in mNSCLC treatment. Our meta-analysis was limited by inconsistent data reporting across subgroups and by the lack of time-to-event survival data within subgroups.