Influence of Smoking History on the Effectiveness of Immune-checkpoint Inhibitor Therapy for Non-small Cell Lung Cancer: Analysis of Real-world Data

Background/Aim: There is no real-world data in an Asian population to investigate the difference between the outcome of immune-checkpoint inhibitor (ICI) monotherapy and combination therapy for non-small cell lung cancer (NSCLC) based on smoking status. In this study, we investigated the correlation between smoking status and the efficacy of ICI therapy for NSCLC patients. Patients and Methods: This multicentre retrospective study enrolled patients with recurrent or metastatic NSCLC who were treated using ICI therapy between December 2015 and July 2020. We analysed the objective response rate (ORR) of patients who received ICI monotherapy or combination therapy, based on smoking status using Fisher’s exact test, and progression-free survival (PFS) and overall survival (OS) based on smoking status using the Kaplan–Meier method, the log-rank test, and Cox proportional hazards model. Results: A total of 487 patients were included in the study. In the ICI monotherapy group, non-smokers showed significantly lower ORR and shorter PFS and OS than smokers (10% vs. 26%, p=0.002; median: 1.8 vs. 3.8 months, p<0.001; median: 8.0 vs. 15.4 months, p=0.026). In the ICI combination therapy group, non-smokers showed significantly longer OS than smokers (median: not reached vs. 26.3 months, p=0.045), and there was no significant difference in ORR and PFS between non-smokers and smokers (63% vs. 51%, p=0.43; median: 10.2 vs. 9.2 months, p=0.81). In the multivariate analysis of patients who received ICI combination therapy, the “non-smoker” status was not significantly associated with PFS [hazard ratio (HR)=1.31; 95% confidence interval (CI)=0.70-2.45, p=0.40] and OS (HR=0.40; 95% CI=0.14-1.13, p=0.083). Conclusion: Non-smokers showed worse outcomes than smokers with ICI monotherapy, but not with ICI combination therapy.