化疗联合贝伐单抗治疗Her-2阴性乳腺癌有效性和安全性的Meta分析  

Bevacizumab as Salvage Treatment for Her-2 Negative Breast Cancer:A Systematic Review

作　　者：徐龙[1,2] 章国晶[1] 谢晓冬[1] 

机构地区：[1]沈阳军区总医院全军肿瘤诊治中心,沈阳110840 [2]第四军医大学研究生管理大队,西安710032

出　　处：《中国循证医学杂志》2012年第11期1347-1353,共7页Chinese Journal of Evidence-based Medicine

基　　金：辽宁省自然科学基金资助项目(编号:20082070)

摘　　要：目的系统评价化疗联合贝伐单抗治疗Her-2阴性复发或转移性乳腺癌的有效性及安全性。方法计算机检索PubMed、EMbase、The Cochrane Library、SCI引文数据库和CBM数据库,收集采用化疗联合与不联合贝伐单抗治疗Her-2阴性复发或转移性乳腺癌的Ⅲ期临床随机对照试验(RCT),并查阅ASCO、ESMO近三年相关会议摘要和2012年NCCN指南,以及手工检索相关中文期刊,检索时限均截至2012年2月。由2位研究者按照纳入和排除标准独立筛选文献、评价质量并交叉核对,如遇分歧则讨论解决或请专家协商决定而后,采用STATASE 12.0软件进行Meta分析。结果初检出文献132篇,最终纳入4个RCT,共3 131例患者。Meta分析结果显示,与单纯化疗相比,化疗联合贝伐单抗可延长Her-2阴性复发或转移性乳腺癌患者无进展生存期[HR=0.67,95%CI(0.57,0.79),P<0.001],但未能延长总生存期[HR=0.92,95%CI(0.82,1.02),P=0.121];在安全性方面,化疗联合贝伐单抗组患者高血压、蛋白尿、出血不良反应较单纯化疗组增多,而血栓、中性粒细胞减少及感觉障碍发生率方面,两组差异无统计学意义。结论贝伐单抗可延长Her-2阴性复发或转移性乳腺癌患者的无进展生存期,但未能延长总生存期,与单纯化疗相比3至4度不良反应有所增加。今后尚需进一步探索贝伐单抗用于乳腺癌解救治疗的最佳适应人群。Objective To systematically review the effect and safety of bevacizumab as salvage treatment for Her-2 negative recurrent or metastatic breast cancer. Methods The stage III randomized controlled trials （RCTs） on chemo- therapy plus bevacizumab vs. chemotherapy alone for Her-2 negative recurrent or metastatic breast cancer were collected from PubMed, EMbase, The Cochrane Library, SCI citation database and CBM. Conference s in ASCO and ESMO during last three years, NCCN guideline （2012）, as well as relevant Chinese journals were also retrieved manually. The re- trieved literature was published from the inception of databases to February 2012. Two reviewers independently screened the literature according to inclusion and exclusion criteria, evaluated and cross-checked methodological quality, and resolved discrepancy by discussion or according to expert opinion. Then meta-analysis was conducted using STATA SE 12.0 software. Results Of 132 articles collected, a total of 4 RCTs involving 3 131 patients were included. The results of meta-analyses showed that： compared with chemotherapy alone, bevacizumab plus chemotherapy could improve the pro- gression-free survival （PFS） for patients with Her-2 negative breast cancer （HR=0.67, 95%CI 0.57 to 0.79, P=0.001）, but it could not prolong the overall survival （OS） （HR=0.92, 95%CI 0.82 to 1.02, P=0.121）. Adverse effects such as hyperten- sion, proteinuria and bleeding significantly increased in the bevacizumab group, but no statistical significance was found in thrombo-embolic event, neutropenia and sensory neuropathy between the two groups. Conclusion Bevacizumab can improve PFS rather than OS for patients with Her-2 negative recurrent or metastatic breast cancer, and it increases the Grade 3 to 4 adverse effects. It is necessary to identify the best indications of bevacizumab as salvage treatment for breast cancer.

关 键 词：乳腺癌 HER-2 贝伐单抗 随机对照试验 系统评价 META分析 

分 类 号：R737.9[医药卫生—肿瘤]