Meta-analysis Of The Efficacy And Safety Of Neoadjuvant Trastuzumab Combined With Pertuzumab For HER2-positive Breast Cancer

Objective: To evaluate the efficacy and safety of trastuzumab combined with pertuzumab versus trastuzumab in the neoadjuvant treatment for patients with HER2-positive breast cancer,and to provide evidence-based reference for rational use of drugs in clinic.Methods: Retrieved from Pub Med,Embase,Cochrane Library,CNKI and Wanfang database,from database establishment to December 2019,to identify clinical studies about the neoadjuvant trastuzumab and pertuzumab combined with chemotherapeutic drugs for patients with HER2-positive breast cancer.After literature screening and data extraction based on the inclusion and exclusion criteria,the quality of RCTs was evaluated by using the quality evaluation standard of RCTs in Cochrane Systematic Evaluator Manual 5.3,and Newcastle-Ottawa scale was used to evaluate the quality of the retrospective study.Meta-analysis was performed by using Rev Man5.3 software.Results: There were 9 studies finally identified,including 2 RCTs and 7retrospective studies,a total of 2726 patients.Meta-analysis showed that the p CR rate and ORR of trastuzumab+pertuzumab group were significantly better than trastuzumab group(p CR: RR = 1.39,95% CI: 1.27-1.51,P <0.00001;ORR: RR =1.12,95% CI: 1.03-1.22,P = 0.006),but there was no statistical difference in the rate of breast conserving surgery between the two groups(RR = 1.06,95% CI: 0.73-1.52,P = 0.77).Subgroup analysis showed that both in the HR-positive and HR-negative breast cancer,trastuzumab+pertuzumab group could increase the p CR rate more than trastuzumab group(HR-positive group: RR = 1.46,95% CI: 1.10-1.93,P = 0.008;HR-negative group: RR = 1.64,95% CI: 1.31-2.05,P <0.0001),and the effect of dual-target therapy was more significant in HR negative patients(RR = 0.62,95% CI:0.50-0.77,P <0.00001).As for the adverse event,the risk of hair loss,neutropenia,diarrhea,nausea,and infusion-related reactions in the trastuzumab + pertuzumab group was not higher than that in the trastuzumab group.In terms of adverse events above grade 3,there was no significant difference in the incidence of neutropenia,leukopenia,and serious adverse events.Conclusion: In the neoadjuvant treatment of HER2-positive breast cancer,the short-term efficacy of chemotherapy combined with trastuzumab and pertuzumab dual-target treatment is superior to chemotherapy combined with trastuzumab single target treatment,HR-negative patients is more sensitive than HR-positive patients,and dual-targeted therapy does not increase the risk of related adverse events.