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sacituzumab govitecan-hziy治疗难治性转移性三阴性乳腺癌
Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer


Aditya Bardia ... 肿瘤 • 2019.02.21
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抗体药物偶联物治疗晚期三阴性乳腺癌的希望

 

王殊*,刘淼

北京大学人民医院乳腺中心

*通讯作者

 

转移性三阴性乳腺癌(雌激素受体、孕激素受体和人表皮生长因子受体-2阴性)患者的总生存期在过去20年没有任何延长。2019年2月21日出版的《新英格兰医学杂志》(NEJM)发表的《sacituzumab govitecan-hziy治疗难治性转移性三阴性乳腺癌》论著,介绍了抗体-药物偶联物sacituzumab govitecan-hziy在治疗该型乳腺癌取得的可喜进展。

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摘要


背景

在既往接受过治疗的转移性三阴性乳腺癌患者中,标准化疗的缓解率低,无进展生存期短。sacituzumab govitecan-hziy是一种将人源化单克隆抗体与SN-38相结合的抗体-药物偶联物,人源化单克隆抗体靶向作用于人滋养层细胞表面抗原2(Trop-2),SN-38通过可裂解的连接物与抗体偶联。sacituzumab govitecan-hziy可向肿瘤输送高浓度SN-38。

 

方法

我们开展了一项1/2期、单组、多中心试验,在这项试验中,晚期上皮癌患者在每个21日周期的第1日和第8日接受sacituzumab govitecan-hziy静脉给药治疗,直至疾病进展或者出现不可接受的毒性作用。共计108例患者在既往因转移性三阴性乳腺癌接受至少两种抗癌治疗之后,接受了剂量为10 mg/kg的sacituzumab govitecan-hziy治疗。终点包括安全性、当地判定的客观缓解率(根据《实体瘤疗效评价标准》1.1版)、缓解持续时间、临床获益率(定义为完全或部分缓解或者疾病稳定至少6个月)、无进展生存期,以及总生存期。事后分析确定了缓解率和持续时间(通过盲法独立集中审核的方式进行判定)。

 

结果

108例三阴性乳腺癌患者既往接受的治疗种数中位数为3种(范围,2~10种)。治疗期间有4例患者死亡;3例患者(2.8%)因不良事件终止治疗。发生于≥10%患者的3或4级不良事件包括贫血和中性粒细胞减少;10例患者(9.3%)出现了发热性中性粒细胞减少。缓解率(3例完全缓解,33例部分缓解)为33.3%(95%置信区间[CI],24.6~43.1),中位缓解持续时间为7.7个月(95% CI,4.9~10.8);通过独立集中审核判定的相应数值分别为34.3%和9.1个月。临床获益率为45.4%。中位无进展生存期为5.5个月(95% CI,4.1~6.3),总生存期为13.0个月(95% CI,11.2~13.7)。

 

结论

在既往接受过大量治疗的转移性三阴性乳腺癌患者中,sacituzumab govitecan-hziy与持久的客观缓解相关。骨髓毒性作用是主要的不良反应(由Immunomedics资助;IMMU-132-01在ClinicalTrials.gov注册号为NCT01631552)。 





作者信息

Aditya Bardia, M.D., Ingrid A. Mayer, M.D., Linda T. Vahdat, M.D., M.B.A., Sara M. Tolaney, M.D., M.P.H., Steven J. Isakoff, M.D., Ph.D., Jennifer R. Diamond, M.D., Joyce O’Shaughnessy, M.D., Rebecca L. Moroose, M.D., Alessandro D. Santin, M.D., Vandana G. Abramson, M.D., Nikita C. Shah, M.D., Hope S. Rugo, M.D., David M. Goldenberg, Sc.D., M.D., Ala M. Sweidan, M.B.A., M.S., Robert Iannone, M.D., Sarah Washkowitz, J.D., Robert M. Sharkey, Ph.D., William A. Wegener, M.D., Ph.D., and Kevin Kalinsky, M.D.
From the Massachusetts General Hospital Cancer Center (A.B., S.J.I.) and Dana–Farber Cancer Institute (S.M.T.), Harvard Medical School, Boston; Vanderbilt–Ingram Cancer Center, Nashville (I.A.M., V.G.A.); Weill Cornell Medical College (L.T.V.) and New York–Presbyterian–Columbia University Irving Medical Center (K.K.), New York; University of Colorado Cancer Center, Aurora (J.R.D.); Texas Oncology, Baylor University Medical Center, US Oncology, Dallas (J.O.); Orlando Health University of Florida Health Cancer Center, Orlando (R.L.M., N.C.S.); Yale University School of Medicine, New Haven, CT (A.D.S.); University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.); Immunomedics, Morris Plains, NJ (D.M.G., R.I., S.W., R.M.S., W.A.W.); and AIS Consulting, Ann Arbor, MI (A.M.S.). Address reprint requests to Dr. Bardia at the Massachusetts General Hospital Cancer Center, Harvard Medical School, Lawrence House 304, 10 N. Grove St., Boston, MA 02114, or at bardia.aditya@mgh.harvard.edu.

 

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