帕妥珠单抗联合曲妥珠单抗治疗HER-2阳性乳腺癌的Meta分析

Pertuzumab combined with trastuzumab for treatment of HER-2 positive breast cancer: a Meta-analysis

目的:系统评价帕妥珠单抗联合曲妥珠单抗治疗人类表皮生长因子受体2(HER-2)阳性乳腺癌的疗效及安全性,为新药上市及临床使用提供循证参考。方法:计算机检索Cochrane Library,Pub Med,EMbase数据库,收集帕妥珠单抗联合曲妥珠单抗(试验组)对比曲妥珠单抗(对照组)治疗HER-2阳性乳腺癌的临床随机对照试验(randomized controlled trials,RCTs),检索时限均为建库至2018年7月。提取资料并按照Cochrane系统评价员手册5.1.0提供的偏倚风险评估工具评价质量后,采用Rev Man 5.3软件进行Meta分析。结果:最终纳入个5项RCTs,包括6536例患者。Meta分析结果显示,与曲妥珠单抗单用相比,联合帕妥珠单抗无进展生存期(progression-free survival,PFS)[风险比(HR)=0.69,95%可信区间(CI,0.60,0.78),P<0.00001]、总生存期(overall survival,OS)[HR=0.72,95%CI(0.59,0.87),P=0.0008]较优;在安全性方面,试验组严重不良(serious adverse event,SAE)事件发生率、≥3级中性粒细胞减少的不良反应发生率与对照组无统计学差异(P>0.05),但≥3级腹泻的发生率高于对照组[相对危险度(RR)=2.42,95%CI(1.96,2.98),P<0.00001]。结论:帕妥珠单抗联合曲妥珠单抗方案疗效显著,但存在一定的不良反应,在临床使用过程中,需要加强不良反应监控。

Objective:To systematically evaluate the efficacy and safety of pertuzumab combined with trastuzumab in the treatment of HER-2 positive breast cancer,and provide evidence-based reference for the marketing and clinical use of new drugs.Methods:The Cochrane Library,Pub Med,and EMbase were searched for randomized controlled trials(RCTs)of pertuzumab in combination with trastuzumab(treatment group)versus trastuzumab(control group)for HER-2 positive breast cancer published from the establishment of the databases until July 2018.Meta-analysis was performed using Rev Man 5.3 software after the data were extracted and quality was evaluated using the bias risk assessment tool provided by Cochrane system evaluator manual 5.1.0.Results:A total of five RCTs were included,including 6536 patients.Based on the RCTs included in this review,compared with trastuzumab alone,trastuzumab combined with pertuzumab showed superiority in the progression-free survival(PFS)[HR=0.69,95%CI(0.60,0.78),P<0.00001]and overall survival(OS)[HR=0.72,95%CI(0.59,0.87),P=0.0008];in terms of safety,there were no significant differences in the incidences of serious adverse events and neutropenia of grade≥3 between the treatment group and the control group(P>0.05),but the incidence of grade≥3 diarrhea was higher than that of the control group[RR=2.42,95%CI(1.96,2.98),P<0.00001].Conclusion:The efficacy of pertuzumab combined with trastuzumab is significant,but there are certain adverse reactions.In clinical practice,it is necessary to strengthen the monitoring of adverse reactions.