Bingjia Li, Xiaoyu Huang, Linlin Fu

Smoking status is associated with the efficacy of non-small cell lung cancer (NSCLC) treatment. Latest clinical trials have depicted the difference in the effectiveness of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors in smokers and nonsmokers. However, the lack of statistical power in these trials prevented a final conclusion. The authors postulated that the efficacy of PD-1/PD-L1 inhibitors correlated with smoking status. Clinical trials evaluating PD-1 inhibitors versus chemotherapies in smokers and nonsmokers were included. The hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were used. A total of 1,981 patients from three Phase III randomized controlled trials (RCTs) were included. PD-1/PD-L1 inhibitors significantly prolonged the OS (HR, 0.69; 95% CI, 0.60-0.78) and PFS (HR, 0.55; 95% CI, 0.43-0.67; P = 0.027) in smoking patients versus chemotherapy. However, among nonsmoking patients, no significant improved OS and PFS were observed compared with chemotherapy. PD-1 inhibitors were more efficacious in smoking NSCLC patients compared with chemotherapy. No better survival of nonsmoking patients was observed in the treatment of PD-1 inhibitors than chemotherapy. Difference in the efficacy of PD-1 treatment should be taken into consideration in the future guidelines and clinical practice.