Meta-analysis Of Related Adverse Events Caused By ICIs Alone Or Combined With Routine Chemotherapy In The Treatment Of NSCLC

Objective: To systematically evaluate the occurrence of related adverse events（AEs）caused by immune checkpoint inhibitors（ICIs）alone or combined with routine chemotherapy in the treatment of non-small cell lung cancer（NSCLC）,and to provide evidence-based reference for clinical medication.Methods: Retrieved from Pub Med,Cochrane Library,Embase,CNKI,CBM,VIP and Wanfang database during the inception to Nov.2021,randomized controlled trials（RCT）about ICIs alone or combined with routine chemotherapy（trial group）versus routine chemotherapy or placebo combined with routine chemotherapy（control group）were collected.After literature screening and data extraction,the quality of included literatures were evaluated with bias risk evaluation tool recommended by Cochrane systematic evaluator manual 5.1.0.Meta-analysis was performed by using Rev Man 5.3software and Stata 15.0 software.Sensitivity analysis was conducted with Stata 15.0software.Inverted funnel plot,Begg’s test and Egger’s test were used to analyze publication bias.Results: A total of 28 RCTs were included in this study,involving 15829 patients,including 8569 in the trial group and 7260 in the control group.The results of metaanalysis showed that the incidence of all-grade and severe AEs,anemia,neutropenia,vomiting,alopecia and all-grade of thrombocytopenia,nausea as well as peripheral neuropathy in trial group were（significantly）lower than control group（P<0.05）.There were no statistical significance in the incidence of death,severe thrombocytopenia,severe nausea and severe peripheral neuropathy as well as all-grade and severe diarrhea between2 groups（P>0.05）.For immune-related adverse events（ir AEs）,the incidence of allgrade and severe rash,pneumonia,colitis,hepatitis,hypothyroidism,nephritis and the all-grade of hyperthyroidism in the trial group were higher than those in the control group（P<0.05）,there was no significant difference in severe hyperthyroidism between the 2groups（P>0.05）.Subgroup analysis showed that the incidence of all grades and severe anemia,neutropenia,thrombocytopenia,clinically relevant symptoms（except for severe diarrhea）,and incidence of all grade and severe AEs and death of patients receiving ICIs alone in trial group were significantly lower than control group（P<0.05）.The incidence of all-grades and severe neutropenia and diarrhoea,all-grades thrombocytopenia,nausea and vomiting,and incidence of all-grade and severe AEs of patients receiving ICIs with chemotherapy in trial group were significantly higher than control group（P<0.05）.For the incidence of ir AEs,except the incidence of severe hyperthyroidism and severe hypothyroidism（there was no significant difference between the trial group and the control group with ICIs alone or ICIs + chemotherapy）,the incidence of other ir AEs in the trial group（ICIs alone / ICIs + chemotherapy）was significantly higher than control group（P<0.05）.Sensitivity analysis supported the above results.Conclusions: The results of this study show that for patients with NSCLC,the safety of ICIs is better than that of routine chemotherapy or placebo combined with routine chemotherapy in the treatment-related AEs,hematologic toxicity and clinically relevant symptoms;However,the risks of overall severe AEs and all-grade neutropenia,thrombocytopenia,nausea vomiting,diarrhea,and severe neutropenia,diarrhea will be increased in the ICIs combined with routine chemotherapy.ICIs leads to special ir AEs in NSCLC patients,and the incidence of ir AEs is generally higher than patients of conventional chemotherapy or placebo combined with conventional chemotherapy.