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

• Published in: World journal of surgical oncology Vol. 18; no. 1; p. 15
• Main Authors: Mo, Jiahang, Hu, Xiao, Gu, Lihu, Chen, Bangsheng, Khadaroo, Parikshit Asutosh, Shen, Zefeng, Dong, Lei, Lv, Yuqi, Chitumba, Marylin Nyaradzo, Liu, Jiequan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.01.2020; BioMed Central; BMC
• Subjects: Anti-PD-1/PD-L1; Bias; Cancer; Cancer therapies; Carcinoma; Care and treatment; Chemotherapy; Clinical trials; Collaboration; Comparative analysis; Confidence intervals; Health aspects; Human papillomavirus; Immune checkpoint inhibitors; Immune system; Immunotherapy; Inhibitors; Lung cancer; Medical research; Melanoma; Meta-analysis; Monoclonal antibodies; Mutation; Non-small cell lung carcinoma; Nonsmokers; On-line systems; Patient outcomes; PD-1 protein; PD-L1 protein; Quality; Review; Small cell lung carcinoma; Smokers; Smoking; Studies; Subgroups; Tumors; China; Anti-PD-1/PD-L1; Immune checkpoint inhibitors; Immunotherapy; Meta-analysis; Smoking
• ISSN: 1477-7819; 1477-7819
• DOI: 10.1186/s12957-020-1792-4

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. 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. 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. 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.