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帕妥珠单抗和曲妥珠单抗辅助治疗早期HER2阳性乳腺癌
Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer


Gunter von Minckwitz ... 肿瘤 • 2017.07.13
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从CLEOPATRA,NeoSphere到APHINITY,双靶向联合化疗能否成为辅助治疗的新标准

 

陈佳艺  

上海交通大学医学院附属瑞金医院放射治疗科

 

从转移性患者一线方案和(或)从新辅助治疗方案着手,验证一个新的药物治疗方案相比标准方案的优势,进而在辅助治疗中证实疗效优势,这是很多新型抗肿瘤治疗方案得到临床验证的美好理想。在不同阶段的HER2阳性乳腺癌疗效已经大大改观的今天,在曲妥珠单抗联合多西他赛的基础上加用帕妥珠单抗,经过了一线、新辅助的阳性结果,能否最终在辅助治疗中得到验证,无疑会受到无数同行的期待。

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摘要


背景

当帕妥珠单抗联合曲妥珠单抗和化疗治疗人表皮生长因子受体2(HER2)阳性乳腺癌时,对于转移性疾病患者,帕妥珠单抗术前用药的情况下可以提高病理完全缓解率,并且可提高生存率。在本项试验中,我们研究了帕妥珠单抗联合曲妥珠单抗和化疗作为辅助治疗能否改善HER2阳性早期乳腺癌患者的结局。

 

方法

我们将淋巴结阳性或高危的淋巴结阴性HER2阳性、可行手术治疗的乳腺癌患者随机分组,分别接受帕妥珠单抗或安慰剂联合标准辅助化疗加为期1年的曲妥珠单抗治疗。我们假设帕妥珠单抗组的3年无浸润性疾病生存率为91.8%,安慰剂组为89.2%。

 

结果

在本试验人群中,经随机分组接受帕妥珠单抗(2,400例)或安慰剂(2,405例)治疗的患者中,63%的病例为淋巴结阳性乳腺癌,36%的病例为激素受体阴性乳腺癌。帕妥珠单抗组有171例(7.1%)患者出现疾病复发,安慰剂组有210例(8.7%)(风险比,0.81;95%置信区间[CI],0.66~1.00;P=0.045)。帕妥珠单抗组估计的3年无浸润性疾病生存率为94.1%,安慰剂组为93.2%。在淋巴结阳性乳腺癌患者队列中,帕妥珠单抗组的3年无浸润性疾病生存率为92.0%,相比之下安慰剂组为90.2%(浸润性疾病事件风险比,0.77;95% CI,0.62~0.96;P=0.02)。在淋巴结阴性乳腺癌患者队列中,帕妥珠单抗组的3年无浸润性疾病生存率为97.5%,安慰剂组为98.4%(浸润性疾病事件风险比,1.13;95% CI,0.68~1.86;P=0.64)。在两个治疗组中,心力衰竭、心源性死亡和心功能障碍均较为少见。等于或大于3级的腹泻几乎都发生在化疗期间,并且在帕妥珠单抗组比安慰剂组常见(9.8%对3.7%)。

 

结论

在可行手术治疗的HER2阳性乳腺癌患者中,当帕妥珠单抗与曲妥珠单抗和化疗联合使用时,可显著提高无浸润性疾病生存率。与安慰剂组相比,腹泻在帕妥珠单抗组较为常见(由霍夫曼-罗氏/基因泰克[Hoffmann-La Roche/Genentech]资助。APHINITY在ClinicalTrials.gov注册号为NCT01358877)。





作者信息

Gunter von Minckwitz, M.D., Marion Procter, Ph.D., Evandro de Azambuja, M.D., Dimitrios Zardavas, M.D., Mark Benyunes, M.D., Giuseppe Viale, M.D., Thomas Suter, M.D., Amal Arahmani, Ph.D., Nathalie Rouchet, M.Sc., Emma Clark, M.Sc., Adam Knott, Ph.D., Istvan Lang, M.D., Christelle Levy, M.D., Denise A. Yardley, M.D., Jose Bines, M.D., Richard D. Gelber, Ph.D., Martine Piccart, M.D., and Jose Baselga, M.D., for the APHINITY Steering Committee and Investigators*
From the German Breast Group, Neu-Isenburg, Germany (G.M.); Frontier Science (Scotland), Kincraig, United Kingdom (M. Procter); the Breast European Adjuvant Study Team (BrEAST) Data Center (E.A., N.R.), the Breast International Group (D.Z., A.A.), and Institut Jules Bordet, Université Libre de Bruxelles (M. Piccart) — all in Brussels; Roche Pharma (M.B., E.C., A.K.) and the Department of Cardiology, Cardio-Oncology, Bern University Hospital (T.S.) — both in Bern, Switzerland; the Department of Pathology, European Institute of Oncology, University of Milan, Milan (G.V.); the National Institute of Oncology, Budapest, Hungary (I.L.); Centre François Baclesse, Caen, France (C.L.); the Sarah Cannon Research Institute and Tennessee Oncology, Nashville (D.A.Y.); Instituto Nacional de Câncer, Rio de Janeiro (J. Bines); Dana–Farber Cancer Institute, Harvard Medical School, Harvard T. H. Chan School of Public Health, and Frontier Science and Technology Research Foundation — all in Boston (R.D.G.); and the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York (J. Baselga). Address reprint requests to Dr. von Minckwitz at the German Breast Group, GBG Forschungs, Martin-Behaim-Str. 12, 63263 Neu-Isenburg, Germany, or at gunter.vonminckwitz@gbg.de, or to Dr. Baselga at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, or at baselgaj@mskcc.org.

 

参考文献

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