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曲妥珠单抗-美坦新偶联物治疗残留浸润性HER2阳性乳腺癌
Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer


Gunter von Minckwitz ... 肿瘤 • 2019.02.14
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摘要


背景

接受新辅助化疗+人表皮生长因子受体2(HER2)靶向治疗后有残留浸润性乳腺癌的患者与无残留癌的患者相比预后较差。曲妥珠单抗-美坦新偶联物(trastuzumab emtansine,T-DM1)是由曲妥珠单抗和细胞毒性药物美坦新(DM1,一种美登素衍生物和微管抑制剂)构成的抗体-药物偶联物,对既往接受过化疗+HER2靶向治疗的转移性乳腺癌患者有益。

 

方法

我们开展了一项3期、开放标签试验,试验纳入接受含紫杉烷类药物(联用或不联用蒽环类药物)和曲妥珠单抗新辅助治疗之后,手术时发现乳腺或腋窝有残留浸润性疾病的HER2阳性早期乳腺癌患者。患者被随机分组,接受14个周期的T-DM1或曲妥珠单抗辅助治疗。主要终点为无浸润性疾病生存期(定义为无同侧浸润性乳腺肿瘤复发、同侧局部区域浸润性乳腺癌复发、对侧浸润性乳腺癌、远处复发或任何原因死亡)。

 

结果

期中分析时,在1,486例被随机分组的患者(T-DM1组743例和曲妥珠单抗组743例)中,T-DM1组91例患者(12.2%)和曲妥珠单抗组165例患者(22.2%)出现了浸润性疾病或死亡。在T-DM1组和曲妥珠单抗组中,3年时无浸润性疾病的患者百分比估计值分别为88.3%和77.0%。与曲妥珠单抗组相比,T-DM1组的无浸润性疾病生存率显著较高(浸润性疾病或死亡的风险比,0.50;95%置信区间[CI],0.39~0.64;P<0.001)。T-DM1组10.5%患者和曲妥珠单抗组15.9%患者的第一起浸润性疾病事件为远处复发。安全性数据与T-DM1的已知安全性一致,与曲妥珠单抗单独治疗相比,与T-DM1相关的不良事件较多。

 

结论

在完成新辅助治疗后有残留浸润性疾病的HER2阳性早期乳腺癌患者中,T-DM1辅助治疗的浸润性乳腺癌复发或死亡风险比曲妥珠单抗单独治疗低50%(由罗氏制药/基因泰克资助;KATHERINE在ClinicalTrials.gov注册号为NCT01772472)。





作者信息

Gunter von Minckwitz, M.D., Chiun-Sheng Huang, M.D., Ph.D., Max S. Mano, M.D., Ph.D., Sibylle Loibl, M.D., Eleftherios P. Mamounas, M.D., Michael Untch, M.D., Ph.D., Norman Wolmark, M.D., Priya Rastogi, M.D., Andreas Schneeweiss, M.D., Andres Redondo, M.D., Ph.D., Hans H. Fischer, M.D., William Jacot, M.D., Ph.D., Alison K. Conlin, M.D., Claudia Arce-Salinas, M.D., Ph.D., Irene L. Wapnir, M.D., Christian Jackisch, M.D., Ph.D., Michael P. DiGiovanna, M.D., Ph.D., Peter A. Fasching, M.D., John P. Crown, M.D., Pia Wülfing, M.D., Zhimin Shao, M.D., Elena Rota Caremoli, M.D., Haiyan Wu, Ph.D., Lisa H. Lam, Pharm.D., David Tesarowski, Ph.D., Melanie Smitt, M.D., Hannah Douthwaite, M.Sc., Stina M. Singel, M.D., Ph.D., and Charles E. Geyer, Jr., M.D. for the KATHERINE Investigators*
From the German Breast Group, Neu-Isenburg (G.M., S.L., H.H.F., P.W.), the Center for Hematology and Oncology Bethanien, Frankfurt (S.L.), the AGO-B and HELIOS Klinikum Berlin-Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), the Arbeitsgemeinschaft Gynäkologische Onkologie – Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen–EMN, Friedrich–Alexander University Erlangen–Nuremberg, Erlangen (P.A.F.), and Mammazentrum Hamburg am Krankenhaus Jerusalem, Hamburg (P.W.) — all in Germany; the National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-S.H.); Instituto do Câncer do Estado de São Paulo, São Paulo (M.S.M.); the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation and Orlando Health University of Florida Health Cancer Center, Orlando (E.P.M.); the NSABP Foundation and Allegheny Health Network Cancer Institute (N.W.) and the NSABP Foundation and University of Pittsburgh Cancer Institute, School of Medicine (P.R.), Pittsburgh; Hospital Universitario La Paz–Instituto de Investigación Hospital Universitario La Paz, Madrid (A.R.); Institut Régional du Cancer de Montpellier, Université de Montpellier, INSERM Unité 1194, Montpellier, France (W.J.); the NSABP Foundation and Providence Portland Medical Center, Portland, OR (A.K.C.); the National Cancer Institute, Mexico City (C.A.-S.); the NSABP Foundation and Stanford University School of Medicine, Stanford (I.L.W.), and Genentech, South San Francisco (L.H.L., D.T., M.S., S.M.S.) — both in California; Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT (M.P.D.); the Ireland Cooperative Oncology Research Group, Dublin (J.P.C.); Fudan University Shanghai Cancer Center (Z.S.) and Roche (China) Holding (H.W.), Shanghai; the Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy (E.R.C.); F. Hoffmann–La Roche, Welwyn Garden City, United Kingdom (H.D.); and the NSABP Foundation and Virginia Commonwealth University Massey Cancer Center, Richmond (C.E.G.). Address reprint requests to Dr. von Minckwitz at the German Breast Group, GBG Forschungs, Martin-Behaim-Str. 12, 63263 Neu-Isenburg, Germany, or at vonminckwitz@gbg.de. *A complete list of the KATHERINE Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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