OBJECTIVES: We aimed to estimate the impact of smoking history on the real-world effectiveness of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy.

METHODS: This retrospective cohort study utilized data from the Cancer Public Library Database under the K-CURE project, covering all registered cancer patients in Korea from 2013 to 2019. The database links cancer registration, mortality data until 2020, and medical check-up and claims data from National Health Insurance (NHI) until 2021. We included all NSCLC patients with a smoking history treated with pembrolizumab, nivolumab, or atezolizumab for second or later lines of treatment. Smoking history was assessed based on the NHI medical check-up data prior to ICI initiation. Adjusted hazard ratios (HRs) for ICI treatment discontinuation and all-cause mortality were estimated using a multivariate Cox regression model, and NSCLC-specific mortality was assessed using the Fine-Gray model, adjusting for demographics, tumor characteristics, and comorbidities.

RESULTS: Of the 7,613 NSCLC patients treated with ICIs in our study, 5,632 (74.0%) were identified as ever-smokers and 1,981 (26.0%) as never-smokers. Ever-smokers, compared to never-smokers, tended to be older (76.5% vs. 65.3% aged over 60 years), predominantly male (96.4% vs. 25.7%), and more frequently diagnosed with squamous histology (39.9% vs. 12.6%). After adjusting for baseline covariates, ever-smokers who initiated ICIs experienced a significantly longer treatment duration than never-smokers (HR 0.87; 95% confidence interval [CI] 0.81-0.95). Despite longer treatment durations in ever-smokers, smoking history showed no significant impact on all-cause mortality (HR 0.93; 95% CI 0.85-1.03) or NSCLC-specific mortality (Subdistribution HR 0.94; 95% CI 0.85-1.04).

CONCLUSIONS: In NSCLC patients treated with ICIs as second or later lines, ever-smokers experienced longer treatment durations than never-smokers. However, smoking history did not significantly affect overall or NSCLC-specific mortality.