Attention on Smoking Status to PD-1/PD-L1 Drugs on Non-Small Lung Cancer Patients

Abstract

Smoking is considered a serious risk factor for developing a large array of cardiopulmonary conditions, in particular, squamous cell carcinoma in non-small cell lung cancer (NSCLC). Smoking cessation has reduced the risk of lung cancers and has benefited cancer patients receiving chemotherapy. While selective chemotherapeutic agents have been developed, analysis of drug efficacy in smoking populations has not been extensively studied. Recently, some clinical trials have shown that smokers with NSCLC have a lower hazard ratio (HR) than that of non-smokers, or heavy smokers have a lower HR than that of light/occasional smokers when receiving chemotherapy. We then looked into these studies, the data in 24 large clinical trials for various chemotherapeutic modalities for NSCLC, including a set of separated data detailing treatment with programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. These studies included 9,498 ever smokers, 1,811 current smokers, and 4,030 never smokers. Based on the analysis, we found that smokers with NSCLC had a better treatment response, and this may not be due to isolated incidents or a result of experimental errors, especially in the case of the patient population treated with PD-1 and PD-L1 inhibitors. Interestingly, the HR values of smokers were significantly lower than that of non-smokers with a P-value of 0.0476. Furthermore, a recent study states that smoking status was suggested as the most important, accessible predictor of the efficacy of single drug in the PD-1/PD-L1 inhibitor family in the treatment of NSCLC patients. Although the data in these trials may not represent the entire picture of the effect of PD-1/ PD-L1 inhibitors in smokers with NSCLC, smoking status may be a potential biomarker for predicting the response of these targeted drugs. Future clinical trials should provide further, detailed analysis on the smoking status and related data on the efficacy of chemotherapeutic regimens for NSCLC.