Smoking history may help predict response to immune checkpoint inhibitors (ICIs) in patients with metastatic non-small cell lung cancer (NSCLC), according to a studypublishedin the Journal of the National Cancer Institute.

Researchers evaluated 644 patients with advanced NSCLC who received ICI monotherapy. There were 105 patients who had never smoked, 375 who were former smokers, and 164 who were current smokers.

The objective response rate (ORR) was highest in current smokers — 28.0%, compared with 23.5% in former smokers and 11.4% in never-smokers.

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After controlling for PD-L1 tumor proportion score (TPS) and other characteristics, smoking status was significantly associated with an increased ORR. Compared with never-smokers, the odds ratio was 2.07 for former smokers (P =.04) and 3.04 for current smokers (P =.003).

Never-smokers had significantly shorter progression-free survival (PFS) than former smokers and current smokers. The median PFS was 2.07 months in never-smokers, 3.65 months in former smokers (hazard ratio [HR], 0.74; P =.01), and 3.68 months in current smokers (HR, 0.60; P <.001). 

Never-smokers also had numerically shorter overall survival (OS) than former smokers and current smokers. The median OS was 9.9 months in never-smokers, 12.9 months in former smokers (HR, 0.85; P =.23), and 13.2 months in current smokers (HR, 0.78; P =.10).

Doubling of smoking pack-years was significantly associated with improved clinical outcomes in multivariable analyses after adjusting for PD-L1 TPS and other characteristics. The odds ratio for ORR was 1.21 (P <.001), the HR for PFS was 0.92 (P <.001), and the HR for OS was 0.94 (P =.01).

“Our analysis suggests that smoking pack-years may provide additional predictive

information above and beyond the routinely assessed PD-L1 TPS,” the researchers wrote. “A detailed smoking history should be collected in future clinical practice to make prompt clinical decisions and to enhance the proportion of patients who may benefit from ICIs.”

Disclosures: This research was supported by the National Cancer Institute and other organizations. The study authors reported no conflicts of interest. Please see the original reference for a full list of disclosures.


Wang X, Ricciuti B, Alessi JV, et al. Smoking history as a potential predictor of immune checkpoint inhibitor efficacy in metastatic non-small cell lung cancer. J Natl Cancer Inst. Published online June 11, 2021. doi:10.1093/jnci/djab116