Target Agents On First Line Therapy Of Advanced HER2-positive Breast Cancer:A Network Meta-analysis

Objective: To compare the efficacy and safety of different target agents on first line treatment of advanced HER2-positive breast cancer.In order to explore the best treatment strategy and guide treatment decisions of these patients.Methods: Pub Med,Embase,Medline,the Cochrane Library,Web of Science databases,CBM,CNKI and wanfang database were searched for eligible studies The literature search was performed up to October 20,2017.Relevant randomized controlled trials that reported the efficacy and safety of target agents on first line therapy of advanced HER2-positive breast cancer were considered.A Bayesian network metaanalysis was implemented to synthesize direct and indirect treatment regimens,and graphically rank these results using the ‘gemtc’ package of R software,which was connected to JAGS.Hazard ratio(HR)with 95% confidence interval(CI)was calculated for overall survival(OS)and progression-free survival(PFS),and odds ratios(OR)with 95% confidence interval(CI)was used to evaluate the efficacy and safety of different therapeutics.Results: According to prespecified inclusion criteria,14 studies including a total of 5715 advanced HER2-positive patients were included in the present study.These results of network meta-analysis revealed that the OS of patients who receive d trastuzumab+pertuzumab+chemotherapy was superior to neratinib+chemotherap y(HR=0.65;95%CI:0.44-0.95),trastuzumab+chemotherapy(HR=0.68;95%CI:0.56-0.83),lapatinib+chemotherapy(HR=0.63;95%CI:0.47-0.83)and chemotherapy(HR=0.51;95%CI:0.39-0.66);The PFS of patients who received trastuzumab+pertuzumab+ ch emotherapy was significantly longer than that of patients who received T-DM1(HR=0.77;95%CI:0.61-0.98),trastuzumab+everolimus+chemotherapy(HR=0.76;95%CI:0.59-0.99),trastuzumab+chemotherapy(HR=0.68;95%:0.58-0.80),lapatinib+ chemotherapy(HR=0.54;95%CI:0.43-0.68)and chemotherapy(HR=0.31;95%CI: 0.25-0.39)alone.The ORR of trastuzumab+pertuzumab+chemotherapy significantl y improved,when compared with T-DM1+pertuzumab(OR=2.0;95%CI:1.2-3.2),TDM1(OR=2.3;95%CI:1.4-3.6),trastuzumab+everolimus+chemotherapy(OR=2.0;95% CI:1.2-3.2),neratinib+chemotherapy(HR=2.1;95%CI:1.2-3.7),trastuzumab+chemothera py(OR=1.8;95%CI:1.3-2.6),lapatinib+chemotherapy(OR=1.8;95%CI:1.2-2.9)and chemotherapy(OR=4.4;95%CI:2.9-6.8).The result of direct comparison is simila r with the result of network meta-analysis.The incidence of diarrhea and rash was higher in patients using trastuzumab+pertuzumab+chemotherapy than patient s using T-DM1+pertuzumab,T-DM1,trastuzumab+chemotherapy and chemotherap y.But nausea,vomiting and fatigue were not significantly increased when comp ared to most treatment measures.According to the results of treatment cumulativ e ranking probabilities,trastuzumab+pertuzumab+chemotherapy had the highest probability of being the best treatment regimen in term of OS,PFS and ORR.Conclusion: 1.Trastuzumab+pertuzumab+chemotherapy is superior to most other treatment strategies in terms of OS,PFS,and ORR,and its side effects are not significantly increased when compared to most other treatment strategies.2.According to the results of treatment cumulative ranking probabilities,trastuzumab+pertuzumab+chemotherapy is the best treatment regimen in term of OS,PFS and ORR.