Impact of smoking status on the efficacy of first-line immune checkpoint inhibitors in Asian patients with advanced non-small cell lung cancer: A meta-analysis.

Abstract

273 Background: Smoking is associated with higher tumor mutational burden and improved responsiveness to immune checkpoint inhibitors (ICIs). Most supporting evidence comes from global trials largely enrolling Western populations, whereas Asian patients have distinct clinical and molecular characteristics, including a higher proportion of never-smokers. Whether smoking status modifies ICI efficacy in Asian patients with advanced non-small cell lung cancer (NSCLC) remains unclear. Methods: A PRISMA-compliant search was conducted in February 2026 across PubMed and Embase to identify eligible studies. Phase III randomized controlled trials (RCTs) evaluating first-line ICI plus chemotherapy versus chemotherapy alone in advanced NSCLC populations conducted in Asia or reporting extractable Asian subgroup data were included. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) stratified by smoking status were extracted as primary outcomes for meta-analysis. Overall objective response rate (ORR) was analyzed as a secondary endpoint using pooled risk ratios (RRs). Random-effects models were used to pool effect estimates with 95% confidence intervals (CIs). Interaction testing was performed to evaluate effect modification by smoking status. Heterogeneity was assessed using the I² statistic. Results: Five phase III RCTs were included. ICIs plus chemotherapy improved OS in both smokers (HR = 0.55; 95% CI: 0.46–0.65) and never-smokers (HR = 0.67; 95% CI: 0.51–0.88), with no statistically significant interaction between smoking status and treatment effect (P for interaction = 0.23). Similarly, PFS benefit was observed in both smokers (HR = 0.49; 95% CI: 0.42–0.57) and never-smokers (HR = 0.51; 95% CI: 0.41–0.64), without evidence of effect modification by smoking status (P for interaction = 0.78). ICIs plus chemotherapy also significantly improved ORR (pooled RR = 1.49; 95% CI: 1.30–1.70). Median OS and PFS were prolonged in ICI combination arms compared with chemotherapy, with consistently longer duration of response observed in ICI-treated patients. Conclusions: First-line ICI-based therapy significantly improves survival and response outcomes in Asian patients with advanced NSCLC irrespective of smoking status. OS and PFS benefits were consistent among smokers, with no statistically significant effect modification, indicating that smoking history does not meaningfully alter the efficacy of ICI-based treatment in this population. Outcome Subgroup Pooled Effect 95% CI P for interaction Overall Survival (OS) Smokers HR 0.55 0.46–0.65 0.23 Never-smokers HR 0.67 0.51–0.88 Progression-Free Survival (PFS) Smokers HR 0.49 0.42–0.57 0.78 Never-smokers HR 0.51 0.41–0.64 Objective Response Rate (ORR) Overall population RR 1.49 1.30–1.70 -