曲妥珠单抗与拉帕替尼联合用于乳腺癌新辅助治疗的随机对照研究的Meta分析

doi:10.3760/cma.j.issn.1673-422X.2015.04.008

摘要/Abstract

摘要： 目的比较单用曲妥珠单抗与曲妥珠单抗和拉帕替尼两药联合在HER2阳性乳腺癌新辅助治疗中的有效性和安全性。方法检索PubMed、MEDLINE、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记录，严格按照纳入与排除标准收集HER2阳性乳腺癌患者使用新辅助化疗联合曲妥珠单抗对比新辅助化疗联合曲妥珠单抗、拉帕替尼双重抗HER2治疗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 5.0软件进行Meta分析。结果最终纳入4项临床随机对照试验，共779例患者符合条件。Meta分析结果显示，曲妥珠单抗联合拉帕替尼组较单独使用曲妥珠单抗组病理完全缓解率显著升高（53.3%∶38.8%，RR=1.39，95%CI为1.20~1.63，P<0.001）；Ⅲ～Ⅳ级不良反应方面，除了联合组的腹泻发生率更高（25.6%∶2.2%，RR=11.54，95%CI为5.69~23.41，P<0.001）以外，其他差异均无统计学意义。结论在HER2阳性乳腺癌患者的新辅助治疗中采用新辅助化疗联合曲妥珠单抗、拉帕替尼的双重抗HER2靶向治疗效果较好，且除了腹泻外并不提高其他不良反应发生率，是一种高效、安全的治疗选择。

关键词: 乳腺肿瘤, 肿瘤辅助疗法, Meta分析, 曲妥珠单抗, 拉帕替尼

Abstract: ObjectiveTo compare the efficacy and safety of trastuzumab versus the combination of trastuzumab and lapatinib added to neoadjuvant chemotherapy in HER2positive breast cancer. MethodsWe searched PubMed, MEDLINE, The Cochrane Library, Web of Science, CNKI, Wanfang datebase and the abstracts of major international conferences in recent 5 years to identify randomized controlled trials which met the inclusion and exclusion criteria. Study selection and analyses were undertaken according to the Cochrane Handbook. Metaanalysis was performed using RevMan 5.0 software. ResultsFour trials were identified with 779 eligible patients. The results of metaanalyses showed that the rate of pathological complete response was significantly higher in the group receiving rastuzumab and tlapatinib than that in the group with trastuzumab alone (53.3%vs 38.8%，RR=1.39, 95 %CI： 1.201.63; P<0.001). No statistical differences were observed in regarding adverse events among patients receiving trastuzumab or the combination of trastuzumab and lapatinib, except the grade ⅢⅣ diarrhea (2.2%vs 25.6%，RR=11.54, 95%CI： 5.6923.41; P<0.001). ConclusionThe combination of trastuzumab and lapatinib added to neoadjuvant chemotherapy in HER2positive breast cancer is more effective, without more adverse reactions except diarrhea; it ia an effective and safe treatment.

Key words: Breast neoplasms, Neoadjuvant therapy, Metaanalysis, Trastuzumab, Lapatinib

曹敏, 武云强, 卢宁, 黄建国. 曲妥珠单抗与拉帕替尼联合用于乳腺癌新辅助治疗的随机对照研究的Meta分析[J]. 国际肿瘤学杂志, 2015, 42(4): 296-273.

CAO Min, WU Yun-Qiang, LU Ning, HUANG Jian-Guo. The combination of trastuzumab and lapatinib added to neoadjuvant chemotherapy for breast cancer: a meta-analysis of randomized evidence[J]. Journal of International Oncology, 2015, 42(4): 296-273.

参考文献

［1］ Ross JS, Slodkowska EA, Symmans WF, et al. The HER2 receptor and breast cancer: ten years of targeted antiHER2 therapy and personalized medicine［J］. Oncologist, 2009, 14(4): 320368. ［2］ Dawood S, Broglio K, Buzdar AU, et al. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutionalbased review［J］. J Clin Oncol, 2010, 28(1): 9298. ［3］ Valachis A, Mauri D, Polyzos NP, et al. Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2positive breast cancer: a systematic review and metaanalysis［J］. Breast, 2011, 20(6): 485490. ［4］ Viani GA, Afonso SL, Stefano EJ, et al. Adjuvant trastuzumab in the treatment of her2positive early breast cancer: a metaanalysis of published randomized trials［J］. BMC Cancer, 2007, 7: 153. ［5］ Harris CA, Ward RL, Dobbins TA, et al. The efficacy of HER2targeted agents in metastatic breast cancer: a metaanalysis［J］. Ann Oncol, 2011, 22(6): 13081317. ［6］ Cetin B, Benekli M, Turker I, et al. Lapatinib plus capecitabine for HER2positive advanced breast cancer: a multicentre study of Anatolian Society of Medical Oncology (ASMO)［J］. J Chemother, 2014, 26(5): 300305. ［7］ Jackisch C, Scappaticci FA, Heinzmann D, et al. Neoadjuvant breast cancer treatment as a sensitive setting for trastuzumab biosimilar development and extrapolation［J］. Future Oncol, 2014, 8(28): 6171. ［8］ Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2positive locally advanced breast cancer (NOAH): followup of a randomised controlled superiority trial with a parallel HER2negative cohort［J］. Lancet Oncol, 2014, 15(6): 640647. ［9］ Badwe R, Hawaldar R, Parmar V, et al. Singleinjection depot progesterone before surgery and survival in women with operable breast cancer: a randomized controlled trial［J］. J Clin Oncol, 2011, 29(21): 28452851. ［10］ Higgins JP, Altman DG, Gtzsche PC, et al. The Cochrane Collaboration′s tool for assessing risk of bias in randomised trials［J］. BMJ, 2011, 343:d5928. ［11］ Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2positive early breast cancer (NeoALTTO): a randomised, openlabel, multicentre, phase 3 trial［J］. Lancet, 2012, 379(9816): 633640. ［12］ Guarneri V, Frassoldati A, Bottini A, et al. Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2positive operable breast cancer: results of the randomized phase Ⅱ CHERLOB study［J］. J Clin Oncol, 2012, 30(16): 19891995. ［13］ Robidoux A, Tang G, Rastogi P, et al. Lapatinib as a component of neoadjuvant therapy for HER2positive operable breast cancer(NSABP protocol B41): an openlabel, randomised phase 3 trial［J］. Lancet Oncol, 2013, 14(12): 11831192. ［14］ Holmes FA, Espina V, Liotta LA, et al. Pathologic complete response after preoperative antiHER2 therapy correlates with alterations in PTEN, FOXO, phosphorylated Stat5, and autophagy protein signaling［J］. BMC Res Notes, 2013, 6: 507. ［15］ Konecny GE, Pegram MD, Venkatesan N, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER2overexpressing and trastuzumabtreated breast cancer cells［J］. Cancer Res, 2006, 66(3): 16301639. ［16］ Wang YC, Morrison G, Gillihan R, et al. Different mechanisms for resistance to trastuzumab versus lapatinib in HER2positive breast cancersrole of estrogen receptor and HER2 reactivation［J］. Breast Cancer Res, 2011, 13(6): R121. ［17］ Blackwell KL, Burstein HJ, Storniolo AM, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2positive metastatic breast cancer: final results from the EGF104900 Study［J］. J Clin Oncol, 2012, 30(21): 25852592. ［18］ Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2positive breast cancer (NeoSphere):a randomised multicentre, openlabel, phase 2 trial［J］. Lancet Oncol, 2012, 13(1): 2532. ［19］ Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer［J］. N Engl J Med, 2012, 366(2): 109119. ［20］ Untch M, Fasching PA, Konecny GE, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups［J］. J Clin Oncol, 2011, 29(25): 33513357. ［21］ Doval DC, Dutta K, Batra U, et al. Neoadjuvant chemotherapy in breast cancer: review of literature［J］. J Indian Med Assoc, 2013, 111(9): 629631.

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