Efficacy And Safety Of Anti PD-1 Antibodies In The Treatment Of Advanced Melanoma: A Meta-analysis

Objective:To systematically evaluate the efficacy and safety of anti-PD-1monoclonal antibody in the treatment of advanced melanoma.Methods:1.Search data on PubMed,EMbase,The Cochrane Libra ry,Wanfang,CNKI,VIP and other databases,using melanoma as a combination of thematic terms and free words.The time limit for searching was from the database to January 19,2018.The type of literature research was Randomized Controlled Trials(RCT);the sea rched documents were screened according to the established literatur e inclusion criteria and exclusion criteria,and the criteria document s were selected.2.Outcome measures were objective response rate(ORR),medi an progression-free survival(PFS),median overall survival(OS),2-year overall survival(OS),and the incidence of treatment-related ad verse events and Grade 3-4 adverse events incident rate.3.The quality of RCT literature was independently assessed by two authors(Zhang Can,Liang Liang).Independently extract data,screen the literature,and use the quality assessment scale JADA s coring method to evaluate the included studies.4.Rev Man 5.3 is using for meta analysis.If the analyzed ind ex is a binary variable,the odds ratio(OR)odds ratio and the rela tive risk(RR)combined effect can be selected.The survival analysis uses the HR(hazard ratio)merger effect.The 95%confidence inte rval CI was eventually chosen.The I~2 test was used for quantitative analysis.RESULTS:1.Seven studies were included and divided into 3subgroups;A total of 4190 patients were included;nivolumab/pembrolizumab with chemotherapy,nivolumab with ipilimumab,nivolumab-plus-ipilimumab with ipilimumab.2.Meta-analysis of the efficacy of the anti-PD-1 monoclonal antibody and chemotherapy group:ORR in the anti-PD-1 monoclonal antibody group(RR=3.28,95%CI(2.46,4.38),P=0.00001)and PFS(HR=0.63,95%CI(0.39,1.01),P=0.05)was superior to the first-line chemotherapy group,and the difference was statistically significant;whereas in the median OS(HR=0.81,95%CI(0.57,1.14,P)(P=0.22)and 2-year OS(RR=1.20,95%CI(0.98,1.47,P=0.08),the difference was not statistically significant;safety:the incidence of adverse reactions(OR=0.98,95%There was no statistically significant difference in the incidence of adverse events(CI=0.43,2.25,P=0.97)and 3-4(OR=0.77,95%CI(0.50,1.18),P=0.23).3.The results of the meta-analysis of the efficacy of the anti-PD-1mAb group versus the Ipilmumab group:ORR in the anti-PD-1 mAb group(RR=2.54,95%CI(2.07,3.11),P=0.00001 and PFS(HR=0.58,95%CI(0.48,0.69),P=0.00001)and median OS(HR=0.66,95%CI(0.57,0.78),P=0.00001)and 2-year OS(RR=1.29,95%CI(1.15,1.45),P=0.00001)were better than Ipilmumab group,the difference was statistically significant;safety aspects:the incidence of adverse reactions(OR=0.99,95%CI(0.69,1.42),P=0.97)There was no statistically significant difference between the two groups;the incidence of 3-4adverse reactions in the anti-PD-1 monoclonal antibody group(OR=0.47,95%CI(0.26,0.85),P=0.01)was better than that of the Ipilmumab group.Meaning.4.Anti-PD-1 monoclonal antibody combined with Ipilmumab group and Ipilmumab group in the effectiveness of the meta-analysis:ORR of anti-PD-1 monoclonal antibody combined with Ipilmumab group(RR=3.36,95%CI(2.64,4.28),P=0.00001)and PFS(HR=0.42,95%CI(0.32,0.54),P=0.00001)and median OS(HR=0.57,95%CI(0.47,0.69)and 2 years OS(RR=1.38,95%CI(1.21,1.58),P=0.00001),P=0.00001)was superior to Ipilmumab group,and the difference was statistically significant;safety:in the incidence of adverse reactions(OR=2.69,95%CI(1.56,4.64),P=0.0004)have statistical significance between the two groups;the incidence of grade 3-4 adverse reactions of anti-PD-1 monoclonal antibody combined with Ipilmumab(OR=3.96,95%CI(2.90,5.40),P=0.0001)In the Ipilmumab group,there was statistical significance.Conclusion:1.Compared with first-line chemotherapy,anti-PD-1monoclonal antibody is more effective in the treatment of advanced melanoma.2.Anti-PD-1 monotherapy for advanced melanoma is more effective and safe than Ipilimumab.3.The efficacy of anti-PD-1 monoclonal antibody combined with Ipilmumab in the treatment of advanced melanoma is superior to that of the Ipilmumab group.