Smoking history and the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis

BACKGROUND: Some studies imply a strong correlation between smoking history and the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Hence, a systematic review and meta-analysis was conducted to comprehensively investigate this correlation. METHODS: Three online databases including PubMed, Embase and Cochrane Library were searched. Abstracts and presentations from European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) were also reviewed. The deadline of search was Nov 9, 2019. Randomized clinical trials (RCT) of ICIs that reported hazard ratio (HR) for overall survival (OS) or progressive-free survival (PFS) by the smoking status of NSCLC patients were eligible for our study. We focused on publications issued in English. A random effects model was implemented in the synthesis, and a two-step interaction test was used to investigate the difference of ICIs efficacy among patients with different smoking histories. RESULTS: Twelve RCTs involving 6,497 NACLC patients [5,569 (85.72%) current/former smokers and 928 (114.28%) never smokers] were eligible for our systematic review and meta-analysis. The pooled HRs [95% confidential interval (CI)] of OS and PFS were 0.74 (0.67, 0.81) and 0.72 (0.59, 0.88) respectively for current/former smokers in the experimental group with ICIs versus those in the control group. The pooled HRs (95% CI) of OS and PFS were 0.81 (0.60, 1.08) and 0.92 (0.55, 1.54) respectively for never smokers in the experimental group with ICIs compared with those in the control group. The difference of ICIs efficacy in terms of OS between current/former and never smokers was insignificant [interaction HR (95% CI), 0.77 (0.69, 0.86), I(2)=25.4%, P_hetero=0.21]. CONCLUSIONS: The efficacy of ICIs in patients with smoking history is seemingly superior over patients without smoking history, but insignificantly. The difference can be explained by several factors such as insufficient sample size of non-smokers, and confounding factors. We suggest that smoking history cannot be recognized as a predictor of immune therapy in advanced NSCLC.