Abstract
Immune checkpoint inhibitors (ICIs) have emerged as a new treatment option for patients with advanced non-small-cell lung cancer (NSCLC). Some studies with ICIs in NSCLC suggested that smoking history was associated with improved survival outcomes. We conducted this meta-analysis to investigate if survival benefits of ICIs in patients with advanced NSCLC are different according to smoking status. Electronic databases were searched for eligible studies. We included randomized controlled trials with the data of survival outcomes and extracted progression-free survival (PFS) or overall survival (OS) stratified by smoking status. From 6 studies, 2,389 ever-smokers and 413 never-smokers were included in the meta-analysis. In first-line treatment setting, ICIs tended to improve PFS in patients with smoking history (HR = 0.85 [95% CI, 0.71–1.10], P = 0.07). For never-smokers with advanced NSCLC, chemotherapy, not ICIs, was significantly associated with improvement of PFS (HR = 2.30 [95% CI, 1.23–4.28], P = 0.009). In more than second-line setting, ICIs significantly prolonged OS over that with chemotherapy in ever-smokers (HR = 0.70 [95% CI, 0.63–0.79], P < 0.00001). For never-smokers with NSCLC, however, ICIs failed to significantly improve OS (HR = 0.79 [95% CI, 0.59–1.06], P = 0.12). In conclusion, this meta-analysis indicates that ICIs can prolong survival over that with chemotherapy in ever-smokers with advanced NSCLC. However, ICIs failed to improve survival in never-smokers. These results suggest that smoking status may be a predictive marker for survival benefits to ICIs.
Highlights
Lung cancer is the leading cause of cancer-related death all over the world [1, 2]
After the meta-analysis, we found that Immune checkpoint inhibitors (ICIs) induced 30 % reduction of the death risk in ever-smokers with advanced non-small-cell lung cancer (NSCLC) (HR = 0.70 [95% confidence intervals (CIs), 0.63–0.79], P < 0.00001) (Figure 3A)
There was no significant heterogeneity (X2 = 2.17, P = 0.34, I2 = 8%). In this meta-analysis, we investigated whether survival benefits of ICIs in advanced NSCLC were different between ever-smokers and never-smokers
Summary
Lung cancer is the leading cause of cancer-related death all over the world [1, 2]. Tobacco smoking has been known as one of the predominant risk factors for lung cancer [3]. ICIs have shown clinical benefits in cancer patients, but there is a great need to identify candidates who will respond to ICIs. Some studies showed the correlation between the efficacy of ICIs and PD-L1 expression on tumor cells and/ or tumor-infiltrating immune cells [10, 11, 13]. Tumor mutational load has been proposed as a possible marker for response to ICIs in NSCLC [17, 18]. Subgroup analysis of clinical trials with anti-PD-1 mAbs (nivolumab or pembrolizumab) in NSCLC suggested that smoking history was associated with improved survival outcomes [12, 15]. In the studies with an anti-PD-L1 mAb (atezolizumab), the overall survival benefit of ICIs over chemotherapy (docetaxel) was observed irrespective of smoking status [13, 14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
