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浙江大学学报(医学版)  2016, Vol. 45 Issue (4): 379-386    DOI: 10.3785/j.issn.1008-9292.2016.07.08
癌分子医学专题     
贝伐珠单克隆抗体联合化疗用于Her2阴性乳腺癌患者新辅助治疗的meta分析
韩瑞, 王冠英, 张玉姣, 赵新汉
西安交通大学医学院第一附属医院肿瘤内科, 陕西 西安 710061
Efficacy of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer: a meta-analysis of randomized controlled clinical trials
HAN Rui, WANG Guanying, ZHANG Yujiao, ZHAO Xinhan
Department of Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
全文: PDF(1018 KB)  
摘要: 

目的:评价贝伐珠单克隆抗体(贝伐珠单抗)联合化疗在Her2阴性乳腺癌患者新辅助治疗中的有效性和安全性。方法:检索PubMed、the Cochrane Library、Web of Science、中国期刊全文数据库、万方医药期刊全文数据库和近5年重要国际肿瘤学会议摘要,严格按照纳入与排除标准收集Her2阴性乳腺癌患者使用新辅助化疗联合贝伐珠单抗(联合组)对比单用新辅助化疗(化疗组)的有效性和安全性的前瞻性随机对照研究。按Cochrane系统评价方法进行质量评价,资料提取后运用RevMan 5.3软件进行meta分析。结果:最终纳入六项随机对照临床试验,共4440例患者符合条件。Meta分析结果显示,联合组较化疗组病理完全缓解率有所提高(24.7%与20.1%,RR=1.23,95%CI:1.10~1.37,P<0.01);联合组无论激素受体是否阳性均可提高病理完全缓解率(激素受体阳性亚组:13.1%与10.2%,RR=1.28,95%CI:1.04~1.58,P<0.05;激素受体阴性亚组:46.3%与37.1%,RR=1.25,95%CI:1.12~1.39,P<0.01);联合组高血压(3.2%与0.6%,RR=5.292,95%CI:2.933~9.549,P<0.01)、黏膜炎(10.5%与2.0%,RR=5.340,95%CI:3.743~7.617,P<0.01)的发生率更高,其他不良反应如中性粒细胞减少性发热、感染、手术并发症、中性粒细胞减少、手足综合征联合组的发生率均高于化疗组(均P<0.05),而周围神经病变发生率两组间差异并无统计学意义(P>0.05)。结论:在Her2阴性乳腺癌患者的新辅助治疗中,不论患者激素受体阳性与否,采用新辅助化疗联合贝伐珠单抗靶向治疗效果较好,但一些不良反应发生率也相应增加,需要更多的临床研究来筛选出优势人群。

关键词 Meta分析乳腺肿瘤/药物疗法抗体,单克隆/治疗应用受体,表皮生长因子/分析化学疗法,辅助    
Abstract

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer.Methods: We searched PubMed, the Cochrane Library, Web of Science, CNKI, Wanfang Database and the abstracts of major international conferences in recent 5 years to identify prospective randomized controlled clinical trials that met the inclusion and exclusion criteria. Study selection and analyses were undertaken according to the Cochrane Handbook. Meta-analysis was performed using RevMan 5.3 software.Results: Six trials were identified with 4440 eligible patients. The results of this meta-analysis showed that the rate of pathological complete response (pCR) was higher in Her-2 negative breast cancer patients receiving bevacizumab combined with neoadjuvant chemotherapy than that in patients with neoadjuvant chemotherapy alone (24.7% vs 20.1%, RR=1.23, 95%CI:1.10-1.37, P<0.01). In addition, the pCR rate rose up when bevacizumab was added to neoadjuvant chemotherapy both in hormone receptor-positive patients (13.1% vs 10.2%,RR=1.28, 95%CI:1.04-1.58,P<0.05) and in hormone receptor-negative patients (46.3% vs 37.1%, RR=1.25, 95%CI:1.12-1.39, P<0.01). Statistical differences were observed in the rate of relevant adverse events such as hypertention (3.2% vs 0.6%, RR=5.292, 95%CI:2.933-9.549, P<0.01) and mucositis (10.5% vs 2.0%, RR=5.340, 95%CI:3.743-7.617, P<0.01) between the combination group and the chemotherapy alone group. Differences in other toxicities such as febrile neutropenia, infection, surgical complications, neutropenia and hand-foot syndrome were also found to be statistically significant between the combination group and the chemotherapy alone group (all P<0.05), while such difference was not found in the occurrence of peripheral neuropathy (P>0.05). Conclusion: The addition of bevacizumab to neoadjuvant chemotherapy in Her2-negative breast cancer can significantly improve pathological complete response, but may bring more grade 3 and 4 toxicities.More neoadjuvant trials need to be done to define subgroups of Her2-negative breast cancer that would have clinically significant long-term benefit from bevacizumab treatment.

Key wordsMeta-analysis    Breast neoplasms/drug therapy    Antibodies, monoclonal/therapeutic use    Receptor, epidermal growth factor/analysis    Chemotherapy, adjuvant
收稿日期: 2016-06-03
CLC:  R686  
通讯作者: 赵新汉(1964-),男,博士,教授,博士生导师,主要从事肿瘤综合治疗和靶向基因治疗研究;E-mail:zhaoxinhanprof@163.com;http://orcid.org/0000-0002-8525-4178     E-mail: zhaoxinhanprof@163.com
作者简介: 韩瑞(1991-),女,博士研究生,主要从事肿瘤综合治疗和靶向基因治疗研究;E-mail:13119190368@163.com;http://orcid.org/0000-0003-2612-3570
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引用本文:

韩瑞 等. 贝伐珠单克隆抗体联合化疗用于Her2阴性乳腺癌患者新辅助治疗的meta分析[J]. 浙江大学学报(医学版), 2016, 45(4): 379-386.
HAN Rui, WANG Guanying, ZHANG Yujiao, ZHAO Xinhan. Efficacy of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer: a meta-analysis of randomized controlled clinical trials. Journal of ZheJiang University(Medical Science), 2016, 45(4): 379-386.

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http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2016.07.08      或      http://www.zjujournals.com/xueshu/med/CN/Y2016/V45/I4/379

[1] FISHER B, BROWN A, MAMOUNAS E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18[J]. J Clin Oncol, 1997, 15(7):2483-2493.
[2] FISHER B, BRYANT J, WOLMARK N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer[J]. J Clin Oncol, 1998, 16(8):2672-2685.
[3] GIANNI L, BASELGA J, EIERMANN W, et al. Phase Ⅲ trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer[J]. J Clin Oncol, 2009, 27(15):2474-2481.
[4] HUNT K K, YI M, MITTENDORF E A, et al.Sentinel lymph node surgery after neoadjuvant chemotherapy is accurate and reduces the need for axillary dissection in breast cancer patients[J]. Ann Surg, 2009, 250(4):558-566.
[5] BEAR H D, ANDERSON S, SMITH R E, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27[J]. J Clin Oncol, 2006, 24(13):2019-2027.
[6] LIEDTKE C, MAZOUNI C, HESS K R, et al.Response to neoadjuvant therapy and longterm survival in patients with triple-negative breast cancer[J]. J Clin Oncol, 2008, 26(8):1275-1281.
[7] KONG X, MORAN M S, ZHANG N, et al.Meta-analysis confirms achieving pathological complete response after neoadjuvant chemotherapy predicts favourable prognosis for breast cancer patients[J]. Eur J Cancer, 2011, 47(14):2084-2090.
[8] VON MINCKWITZ G, KVMMEL S, VOGEL P, et al. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase Ⅲ randomized GeparTrio trial[J]. J Natl Cancer Inst, 2008, 100(8):542-551.
[9] MILLER K, WANG M, GRALOW J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer[J]. N Engl J Med, 2007, 357(26):2666-2676.
[10] BEAR H D, TAILG G, RASTOGI P, et al.Bevacizumab added to neoadjuvant chemotherapy for breast cancer[J]. N Engl J Med, 2012, 366(4):310-320.
[11] HIGGINS J P, ALTMAN D G, GOTZSCHE P C, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials[J]. BMJ, 2011, 343:d5928.
[12] EARL H M, HILLER L, DUNN J A, et al. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer(ARTemis): an open-label, randomised, phase 3 trial[J]. Lancet Oncol, 2015, 16(6): 656-666.
[13] VON MINCKWITZ G, EIDTMANN H, REZAI M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer[J]. N Engl J Med, 2012, 366(4):299-309.
[14] SIKOV W M, BERRY D A, PEROU C M, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage Ⅱ to Ⅲ triple-negative breast cancer: CALGB 40603(Alliance)[J]. J Clin Oncol, 2015, 33(11):13-21.
[15] ENGEBRAATEN O, VASKE C, KROHN M, et al. Molecular response in breast cancer tumors treated with neoadjuvant chemotherapy with and without bevacizumab: results from NeoAva-A randomized phase Ⅱ study[abstract][J]. Cancer Res, 2013, 73(24 Suppl): Abstract nr P4-14-02.
[16] HURVITZ S A, HEGDE P, BOSSERMAN L, et al. Molecular changes in breast tumors following bevacizumab-based treatment: final analysis of a randomized neoadjuvant study of bevacizumab or placebo, followed by chemotherapy with or without bevacizumab, in patients with stage Ⅱ or Ⅲ breast cancer[abstract][J]. Cancer Res, 2012, 72(8 Suppl):Abstract nr 1385.
[17] MIEOG J S, VAN DER HAGE J A, VAN DE VELDE C J.Preoperative chemotherapy for women with operable breast cancer[J]. Cochrane Database Syst Rev, 2007, 18(2):CD005002.
[18] MILLER K, WANG M, GRALOW J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer[J]. N Engl J Med, 2007, 357(26):2666-2676.
[19] MILES D W, CHAN A, DIRIX L Y, et al. Phase Ⅲ study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the firstline treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer[J]. J Clin Oncol, 2010, 28(20):3239-3247.
[20] ROBERT N J, DIÉRAS V, GLASPY J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase Ⅲ trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer[J]. J Clin Oncol, 2011, 29(10):1252-1260.
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