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World J Surg Oncol. 2020 Jan 20;18(1):15. doi: 10.1186/s12957-020-1792-4.

Smokers or non-smokers: who benefits more from immune checkpoint inhibitors in treatment of malignancies? An up-to-date meta-analysis.

Author information

1
The Second Clinical Medical College, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China.
2
School of Stomatology, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China.
3
Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.
4
Emergency Medical Center, The Second Hospital of Yinzhou, 998 North Qianhe Road, Yinzhou District, Ningbo, Zhejiang, 315100, China.
5
Monash University School of Medicine, Nursing and Health Sciences, Melbourne, Australia.
6
Department of Pneumology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China.
7
International Education College, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China.
8
Emergency Medical Center, The Second Hospital of Yinzhou, 998 North Qianhe Road, Yinzhou District, Ningbo, Zhejiang, 315100, China. Yinzhouno1@163.com.

Abstract

BACKGROUND:

Immune checkpoint inhibitors, which are a milestone in anti-cancer therapy, have been applied in the treatment of multiple malignancies. Real-world data have suggested that smoking status may be associated with the efficacy of anti-PD-1/PD-L1 therapy. Hereby, to evaluate "smoking benefit or not", we included numerous high-quality randomized controlled clinical trials (RCTs) without any restriction on category.

METHODS:

A systematic search of online database was performed from July 2010 to July 2019. Eligible studies included phase II/III RCTs comparing PD-1/PD-L1 inhibitors with chemotherapy in the treatment of multiple carcinomas and contained subgroup analysis of smoking status. Then, related hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) were pooled.

RESULTS:

In the initial meta-analysis, compared with chemotherapy, the OS of non-smokers (HR, 0.81; 95% CI, 0.67-0.98) and smokers (HR, 0.77; 95% CI, 0.71-0.83) were significantly prolonged with PD-1/PD-L1 inhibitors. Outcomes from subgroup analysis showed that in anti-PD-1/PD-L1 monotherapy groups, non-smokers showed no significant improvement in OS (HR, 0.94; 95% CI, 0.83-1.06), while the OS of smokers was significantly prolonged (HR, 0.79; 95% CI, 0.74-0.85); in groups of PD-1/PD-L1 inhibitors combined with chemotherapy, the OS of non-smokers (HR, 0.45; 95% CI, 0.28-0.71) and smokers (HR, 0.72; 95% CI, 0.61-0.85) were significantly prolonged. Combined ipilimumab and chemotherapy showed no significance in both groups.

CONCLUSION:

Smokers benefit from either anti-PD-1/PD-L1 monotherapy or the combined regimen compared with chemotherapy. Considering cost-effectiveness, monotherapy was recommended to smokers. For non-smokers, only the combined regimen was feasible in non-small cell lung cancer.

KEYWORDS:

Anti-PD-1/PD-L1; Immune checkpoint inhibitors; Immunotherapy; Meta-analysis; Smoking

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