Efficacy And Safety Of PD-1 Antibody/PD-L1 Antibody Versus Chemotherapy In Advanced Non-small-cell Lung Cancer:a Meta-analysis

Background:Lung cancer is the worlds leading cause of death.Millions of people die of lung cancer every year.Lung cancer is usually classified as non-small cell lung cancer(NSCLC)and small cell lung cancer(SCLC),among which NSCLC is more common,accounting for about 85%.In clinic,most patients with lung cancer have been in advanced stage and lost the opportunity of surgical treatment.They can only control the disease by means of radiotherapy,chemotherapy or targeted therapy.At present,platinum-containing chemotherapy is the standard treatment for advanced lung cancer.In recent years,through the study of the mechanism of tumor immune escape,it has been found that some negative regulatory immunosurveillance sites play an important role in tumorigenesis.Among them,programmed death factor 1(cell death 1,PD-1)and its ligand 1(PD-1 Gilligan,PD-L1)are relatively important immunosurveillance points,They can enhance the resistance of tumor microenvironnent to normal immunity through immune escape,suppression of immune response and avoidance of killing.New drugs for cancer immunotherapy are emerging in endlessly at this immune surveillance site.There are mainly two kinds of antibodies,PD-1 antibody(Nivolumab and Pembrolizumab)and PD-L1(Atezolizumab?Avelumab and Durvalumab)antibody.In recent years,there are more and more reports about the clinical application of immunosuppressive agents in the treatment of advanced non-small cell lung cancer.To further compare the efficacy and safety of PD-1/PD-L1 inhibitors and chemotherapy in the treatment of advanced NSCLC patients,this meta-analysis was performed.Objectives:The aim of this study was to systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of advanced non-small cell lung cancer(NSCLC)compared with chemotherapy,and to provide reference for clinical application.Methods:Search Cochrane Library,Pubmed,Embase,CNKI,Wanfang database,Web of Science and other databases.Time set to 2018.6.1,The types of studies included were defined as clinical randomized controlled trials(RCTs).The extractions included hazard ratio(HR)and 95%confidence interval(CI)of total survival(OS)and progressionfree survival(PFS)of each group,the odds ratio and 95%confidence interval of objective response rate,The total number of adverse reactions,the number of adverse reactions of grade 3 and above,and the number of deaths.The risk ratio(HR)and its 95%confidence interval(CI)were used as the effect analysis statistics for time event data.Bicategorized variables were evaluated by odds ratio(OR)and 95%confidence interval(CI).The statistical analysis software used is Rev Man 5.3.Results:1.Efficacy evaluation:1)In terms of OS,the overall survival rate of PD-1/PD-L1 inhibitor group was higher than that of chemotherapy group,the difference was statistically significant[HR=0.68,95%CI(0.62,0.75),P<0.00001].2)In terms of PFS,The progression-free survival time of PD-1/PD-L1 inhibitor group was higher than that of control group,and the difference was statistically significant[HR=0.80,95%Cl(0.69,0.93),P=0.003].3)In terms of ORR,there were significant differences between the two groups[OR=1.72,95%Cl(1.32,2.25),P<0.0001].2?Safety evaluation:1)In terms of adverse reactions at any level,the adverse events of PD-1/PD-L1 inhibitor group were lower than those of chemotherapy group[OR=0.33,95%Cl(0.28,0.39),P<0.00001].2)In terms of high-level adverse reactions,the high-level adverse reactions in the PD-1/PD-L1 inhibitor group are lower than those in the chemotherapy group[OR=0.20,95%Cl(0.14,0.29),P<0.00001].3)In terms of death events,compared with chemotherapy,PD-1/PD-L1 inhibitors had a lower mortality rate in advanced NSCLC(OR=0.42,95%Cl(0.20,0.89),P=0.02).3?Subgroup analysis results:1)The treatment group with PD-1/PD-L1 inhibitor was compared with the control group.there was no significant difference in the overall survival rate of non-small cell lung cancer(NSCLC)with EGFR mutation[HR=0.88,95%Cl(0.72,1.07),P=0.19].There were significant differences in the overall survival rate of wild-type NSCLC with EGFR[HR=0.68,95%Cl(0.58,0.79),P<0.00001].2)Subgroup analysis based on the difference of PD-L1 expression in patients,There were significant differences in PFS between anti-PD-1/PD-L1 monoclonal antibodies and chemotherapy for non-small cell lung cancer[HR=0.74,95%Cl(0.71,0.78),P<0.00001].especially in the high expression groups of PD-L1?1%[HR=0.81,95%CI(0.74,0.88),P<0.00001]??5%[HR?0.62,95%CI(0.55,0.69),P?0.00001]?? 10%[HR?0.57,95%CI(0.50,0.64),P0.00001],the difference of PFS is significant.Conclusion:1.PD-1/PD-L1 inhibitors are more effective and safer than chemotherapy in the treatment of advanced non-small cell lung cancer.2.PD-1/PD-L1 inhibitors are more effective in the treatment of wild-type non-small cell lung cancer patients with EGFR,and PD-1/PD-L1 antibodies are more effective in the patients with positive or high expression of PD-L1.3.The expression rate of PD-L1 as a diagnostic marker has some reference value,there is still a lack of specific immunodiagnostic markers to maximize the screening of beneficiaries.