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sacituzumab govitecan治疗转移性三阴性乳腺癌
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer


Aditya Bardia ... 肿瘤 • 2021.04.22
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• sacituzumab govitecan-hziy治疗难治性转移性三阴性乳腺癌

ASCENT研究显靶向化疗神威,晚期三阴乳腺癌治疗再添利器

 

刘强

中山大学孙逸仙纪念医院外科;逸仙乳腺肿瘤医院乳腺外科

 

三阴乳腺癌是预后最差的一种乳腺癌,传统化疗是其主要治疗手段,但高达30%左右的早期患者可于手术后短期内复发,且容易对化疗耐药,转移后的中位生存期仅为15-18个月。转移性三阴乳腺癌的治疗是临床上亟待解决的问题。近年来,AR拮抗剂、PARP抑制剂和以PD-1/PD-L1 抗体为基础的免疫治疗的出现,使晚期三阴乳腺癌的治疗方向逐渐走向精准分型和分类治疗。

最近,抗体偶联药物(ADC)也在治疗晚期乳腺癌领域取得突破,针对Trop-2靶点的ADC类药物sacituzumab govitecan(SG)3期临床试验ASCENT [1]结果昨天在《新英格兰医学杂志》(NEJM)发表1,证实了其针对晚期三阴乳腺癌的突出疗效,为晚期三阴乳腺癌治疗再添一强大武器。

sacituzumab govitecan属于第二代ADC类药物,是Trop-2的单克隆抗体和SN-38的偶联物,通过结合三阴乳腺癌细胞表面的Trop-2,在肿瘤局部富集并释放化疗药物SN-38,从而达到精确杀灭肿瘤细胞的目的。ADC类药物好比给化疗药物装上了GPS定位,可以精准打击肿瘤细胞,在提高疗效的同时显著减少了毒副作用,从而与传统化疗的无差别杀伤存在明显不同。

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摘要


背景

转移性三阴性乳腺癌患者的预后不良。sacituzumab govitecan是由靶向人滋养层细胞表面抗原2(Trop-2,在大多数乳腺癌中表达)的抗体通过专利可水解连接子与SN-38(拓扑异构酶Ⅰ抑制剂)偶联后形成的抗体-药物偶联物。

 

方法

此项随机、3期试验在复发性或难治性转移性三阴性乳腺癌患者中比较了sacituzumab govitecan与医师选择的单药化疗(艾立布林、长春瑞滨、卡培他滨或吉西他滨)。主要终点是无脑转移患者的无进展生存期(通过盲法独立集中审核方式判定)。

 

结果

共计468例无脑转移的患者被随机分配接受sacituzumab govitecan(235例患者)或化疗(233例患者)。患者中位年龄为54岁,所有患者均使用过紫杉类药物。sacituzumab govitecan组和化疗组的中位无进展生存期分别为5.6个月(95%置信区间[CI],4.3~6.3;166起事件)和1.7个月(95% CI,1.5~2.6;150起事件)(疾病进展或死亡的风险比,0.41;95% CI,0.32~0.52;P<0.001)。sacituzumab govitecan组和化疗组的中位总生存期分别为12.1个月(95% CI,10.7~14.0)和6.7个月(95% CI,5.8~7.7)(死亡的风险比,0.48;95% CI,0.38~0.59;P<0.001)。sacituzumab govitecan组和化疗组达到客观缓解的患者百分比分别为35%和5%。与治疗相关的3级或更高级别关键不良事件及其发生率如下:中性粒细胞减少(sacituzumab govitecan组51%和化疗组33%)、白细胞减少(10%和5%)、腹泻(10%和<1%)、贫血(8%和5%)和发热性中性粒细胞减少(6%和2%)。两组均有3例患者死于不良事件,患者死亡均被判定为与sacituzumab govitecan不相关。

 

结论

在转移性三阴性乳腺癌患者中,sacituzumab govitecan组的无进展生存期和总生存期显著超过单药化疗组。sacituzumab govitecan组中骨髓抑制和腹泻的发生率较高(由Immunomedics资助,ASCENT在ClinicalTrials.gov注册号为NCT02574455,在EudraCT注册号为2017-003019-21)。





作者信息

Aditya Bardia, M.D., Sara A. Hurvitz, M.D., Sara M. Tolaney, M.D., M.P.H., Delphine Loirat, M.D., Ph.D., Kevin Punie, M.D., Mafalda Oliveira, M.D., Ph.D., Adam Brufsky, M.D., Ph.D., Sagar D. Sardesai, M.D., Kevin Kalinsky, M.D., Amelia B. Zelnak, M.D., Robert Weaver, M.D., Tiffany Traina, M.D., Florence Dalenc, M.D., Philippe Aftimos, M.D., Filipa Lynce, M.D., Sami Diab, M.D., Javier Cortés, M.D., Ph.D., Joyce O’Shaughnessy, M.D., Véronique Diéras, M.D., Cristiano Ferrario, M.D., Peter Schmid, M.D., Ph.D., Lisa A. Carey, M.D., Luca Gianni, M.D., Martine J. Piccart, M.D., Ph.D., Sibylle Loibl, M.D., Ph.D., David M. Goldenberg, Sc.D., M.D., Quan Hong, Ph.D., Martin S. Olivo, M.D., Loretta M. Itri, M.D., and Hope S. Rugo, M.D. for the ASCENT Clinical Trial Investigators*
From the Division of Medical Oncology, Massachusetts General Hospital Cancer Center (A. Bardia), and the Department of Medical Oncology, Dana–Farber Cancer Institute (S.M.T.) — both in Boston; the University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles (S.A.H.); the Medical Oncology Department and the Department of Drug Development and Innovation, Institut Curie, Paris (D.L.), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (F.D.), and the Department of Medical Oncology, Centre Eugène Marquis, Rennes (V.D.) — all in France; the Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven (K.P.), and the Clinical Trials Conduct Unit (P.A.), Institut Jules Bordet–Université Libre de Bruxelles (M.J.P.), Brussels — all in Belgium; the Medical Oncology Department and Breast Cancer Group, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (M.O.), and the International Breast Cancer Center, Quiron Group (J.C.) — all in Barcelona; Magee–Womens Hospital and the Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh (A. Brufsky); Ohio State University Wexner Medical Center, Columbus (S.D.S.); Columbia University Irving Medical Center (K.K.) and Memorial Sloan Kettering Cancer Center (T.T.) — both in New York; Northside Hospital, Atlanta (A.B.Z.); Florida Cancer Specialists, Tampa (R.W.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (F.L.); Rocky Mountain Cancer Centers, Greenwood Village, CO (S.D.); Baylor University Medical Center and Texas Oncology, Dallas (J.O.); Segal Cancer Centre, Jewish General Hospital, Montreal (C.F.); Barts Cancer Institute, Queen Mary University of London, London (P.S.); University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (L.A.C.); Gianni Bonadonna Foundation, Milan (L.G.); the Department of Medicine and Research, Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany (S.L.); Immunomedics, Morris Plains, NJ (D.M.G., Q.H., M.S.O., L.M.I.); and the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.). Address reprint requests to Dr. Bardia at the Massachusetts General Hospital Cancer Center, BHX 237, 55 Fruit St., Boston, MA 02114, or at bardia.aditya@mgh.harvard.edu. *A complete list of the ASCENT Clinical Trial Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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