Meta-analysis of the correlation between immune-related adverse events and efficacy of immune checkpoint inhibitors in the treatment of non-small cell lung cancer / 中国药房

ABSTRACT

OBJECTIVE To sy stematically evaluate the relations hip between immune-related adverse events （irAEs） and efficacy of immune checkpoint inhibitors （ICIs） in the treatment of non-small cell lung cancer （NSCLC），and to provide evidence-based reference for clinical application of ICIs and safety evaluation. METHODS PubMed，Embase，Cochrane Library ， Web of Science ，CNKI，Wanfang database ，VIP and CBM were searched to collect prospective or retrospective cohort studies on the correlation between irAEs and efficacy of ICIs in the treatment of NSCLC. The retrieval time was from the inception to June 30th，2021. After literature screening and data extraction ，Newcastle-Ottawa scale was used to evaluate the quality of included literatures. Meta-analysis and publication bias analysis were performed by using RevMan 5.3 software；Stata 15.0 software was used for sensitivity analysis. RESULTS A total of 7 957 patients were included in 31 studies. Meta-analysis showed that the objective response rate （ORR）[RR＝2.34，95％CI（1.98，2.76），P＜0.000 01]，progression-free survival （PFS）[HR＝0.49，95％CI （0.44，0.55），P＜0.000 01] and overall survival （OS）[HR＝0.45，95％CI（0.39，0.53），P＜0.000 01] of irAEs group as well as ORR[RR＝1.88，95％CI（1.57，2.25），P＜0.000 01]，PFS [HR ＝0.59，95％CI（0.50，0.69），P＜0.000 01] and OS [HR ＝0.58，95％CI （0.48，0.70），P＜0.000 01] of this group at 6th week were all significantly higher or longer than non irAEs group. According to organ specificity ，severity and quantity of irAEs，subgroup analysis showed that skin ，gastrointestinal and endocrine system ，mild irAEs（grade 1-2）and one or more than 2 kinds of irAEs were significantly correlated with the improvement of PFS and OS （P＜ 0.05），while liver and lung ，severe irAEs（≥ grade 3）were not significantly correlated with the improvement of PFS and com OS （P＞0.05）. Sensitivity analysis results showed that the results of the above-mentione d meta-analysis were relatively robust. The results of publication bias showed that there was may be some possibility of publication bias in this study. CONCLUSIONS For NSCLC patients treated with ICIS ，the occurrence of irAEs may be related to their good prognosis. The irAEs may be a predictor of the efficacy of ICIs.