曲妥珠单抗辅助治疗对HER2阳性晚期乳腺癌安全性的Meta分析  

Meta-analysis on safety of Trastuzumab adjuvant therapy in patients with HER2-positive advanced breast cancer

作　　者：甄洪超[1] 李琴[1] 杜琪 赵鹏飞[1] 李莉[1] 蒋晓月 车娟娟[1] ZHEN Hong-chao;LI Qin;DU Qi(Department of Oncology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院肿瘤科

出　　处：《临床和实验医学杂志》2020年第1期43-47,共5页Journal of Clinical and Experimental Medicine

基　　金：国家自然科学基金资助项目(编号:81301912);北京市“215”高层次卫生人才资助项目(编号:2014-3-005);首都医科大学附属北京友谊医院科研启动基金资助项目(编号:yyqdkt2017-19)

摘　　要：目的系统评价曲妥珠单抗辅助治疗在人表皮生长因子受体2(HER2)阳性晚期乳腺癌中的安全性,以期为临床用药积累更多的经验。方法以"晚期乳腺癌"、"HER-2阳性"、"曲妥珠单抗"、"赫赛汀"、"辅助治疗"和"随机对照临床试验"为中文关键词,以"Advanced breast cancer"、"HER-2 positive"、"Trastuzumab"、"Herceptin"、"Adjuvant therapy"和"Randomized controlled trial,RCT"为英文关键词,在中国知网数据库(CNKI)、万方数据库、Pub Med、Embase、Cochrane Library等中英文数据库中检索国内外从建库截止到2019年5月发表的曲妥珠单抗联合其他药物(试验组)对比其他药物(对照组)治疗HER2阳性晚期乳腺癌的前瞻性随机对照临床试验(RCT),对符合纳入标准的研究以Jadad质量计分法对纳入的文献进行质量评估,采用Stata 12.0软件进行Meta分析,评价内容为曲妥珠单抗辅助治疗的安全性,利用Egger’s检验评价发表偏倚。结果共纳入13个RCT研究,合计3127例患者。Meta分析结果显示,在心脏相关的安全性方面,试验组3~4级心脏事件(RR=3.46,95%CI:1.92~6.24,P<0.001)、左室射血分数(LVEF)下降(RR=2.25,95%CI:1.24~4.06,P=0.007)和充血性心力衰竭(CHF)(RR=4.12,95%CI:1.80~9.41,P=0.001)的发生率均显著高于对照组。对于非心脏相关的安全性评价结果显示,试验组血小板减少的发生率显著低于对照组(RR=0.34,95%CI:0.13~0.84,P=0.020),而3~4级中性粒细胞减少、中性粒细胞减少性发热、贫血、乏力、肝功能异常、呕吐、水肿、腹泻等不良反应的发生率两者之间差异无统计学意义(P>0.05)。结论曲妥珠单抗辅助治疗方案应用于HER2阳性晚期乳腺癌患者可导致其心脏不良反应的发生率显著增加,用药过程中需对患者的心脏功能密切监测。Objective To evaluate the safety of Trastuzumab(TRA)adjuvant therapy in treatment of patients with positive human epidermal growth factor receptor 2(HER2)advanced breast cancer,in order to accumulate more experience for clinical medication.Methods The following keywords were used:"Advanced breast cancer","HER-2 positive","Trastuzumab","Herceptin","Adjuvant therapy"and"Randomized controlled trial(RCT)".Several databases including CNKI,Wanfang,Pub Med,Embase and Cochrane Library were searched for randomized controlled trials(RCT)from establishment to May 2019 in comparing the safety of TRA combined with other drugs(trial group)versus other drugs(control group)in the treatment of HER2-positive advanced breast cancer patients.The quality of the studies that met inclusion criteria were assessed by Jadad grading standard and Stata 12.0 software was used for Meta-analysis.The content of evaluation was the safety of TRA adjuvant therapy.Egger’s test was used to evaluate the publication bias.Results Thirteen RCTs were included and 3127 patients were enrolled in the study.In terms of cardiac safety,the pooled analysis demonstrated that the trial group bore a higher incidence of grade 3~4 cardiac events(RR=3.46,95%CI:1.92~6.24,P<0.001),left ventricular ejection fraction(LVEF)decreased(RR=2.25,95%CI:1.24~4.06,P=0.007)and congestive cardiac failure(CHF)(RR=4.12,95%CI:1.80~9.41,P=0.001)compared to control group.For the safety evaluation of non-cardiac toxicity,thrombocytopenia incidence possessed a lower rate in trial group(RR=0.34,95%CI:0.13~0.84,P=0.020)compared to control group.But the incidence rates of grade 3-4 adverse reactions such as neutropenia,febrile neutropenia,anaemia,fatigue,liver dysfunction,vomiting,edema and diarrhea did not exhibit any significant difference between these two groups(P>0.05).Conclution The cardiac toxicity of TRA adjuvant therapy was increased in HER-2 positive patients with advanced breast cancer,and it should be carefully monitored during the therapeutic course.

关 键 词：晚期乳腺癌 HER2阳性 曲妥珠单抗 辅助治疗 安全性 META分析 

分 类 号：R737.9[医药卫生—肿瘤]