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非转移性去势抵抗性前列腺癌患者经恩扎卢胺治疗的生存期
Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer


Cora N. Sternberg ... 肿瘤 • 2020.06.04
相关阅读
• 口服relugolix用于晚期前列腺癌的雄激素剥夺治疗 • 转移性去势抵抗性前列腺癌的恩扎卢胺耐药 • 恩扎卢胺治疗仅前列腺特异性抗原升高的去势抵抗性前列腺癌

新药研发理念创新正在改变前列腺癌的临床诊疗模式

 

高旭*,李晶

上海长海医院泌尿外科

*通讯作者

 

雄激素剥夺治疗(androgen deprivation therapy,ADT)指任何去除雄激素和抑制雄激素活性的治疗方法。作为晚期前列腺癌最重要、最有效的治疗手段,ADT治疗历经了80余年的临床实践检验,现今已然成为公认的药物治疗“基石”,在各种不同分期前列腺癌的治疗环节中发挥重要作用1。根据治疗机制不同,前列腺癌的ADT治疗可以分为四种方式,其中“药物去势”和“雄激素受体拮抗”是临床使用最广、药物选择最多的两种方式(另外两种分别是外科去势和雄激素合成抑制)。

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摘要


背景

初步试验结果表明,在接受雄激素剥夺治疗期间前列腺特异性抗原(PSA)水平迅速升高的非转移性去势抵抗性前列腺癌患者中,恩扎卢胺显著改善了无转移生存期。总生存期的最终分析结果尚未发表。

 

方法

在这项双盲、3期试验中,我们以2∶1的比例将继续接受雄激素剥夺治疗的非转移性去势抵抗性前列腺癌(根据常规影像学检查和PSA倍增时间≤10个月定义)患者随机分组,分别接受每日1次恩扎卢胺(剂量为160 mg)或安慰剂治疗。我们利用成组序贯检验方法和O'Brien-Fleming型α消耗函数评估了总生存期。

 

结果

截至2019年10月15日,共有恩扎卢胺组933例患者中的288例(31%)和安慰剂组468例患者中的178例(38%)死亡。恩扎卢胺组和安慰剂组中的中位总生存期分别为67.0个月(95%置信区间[CI],64.0~未达到)和56.3个月(95% CI,54.4~63.0)(死亡的风险比,0.73;95% CI,0.61~0.89;P=0.001)。在恩扎卢胺组和安慰剂组中,根据药物暴露校正的3级或更高级别不良事件的发生率分别为17起事件/100患者-年和20起事件/100患者-年。恩扎卢胺组的不良事件与之前报告的恩扎卢胺的不良事件一致;最常报告的事件为疲劳和肌肉骨骼事件。

 

结论

在PSA水平迅速升高的非转移性去势抵抗性前列腺癌患者中,与安慰剂+雄激素剥夺治疗相比,恩扎卢胺+雄激素剥夺治疗延长了患者的中位总生存期。与恩扎卢胺相关的死亡风险比安慰剂低27%。不良事件符合恩扎卢胺的已知安全性(由辉瑞制药和安斯泰来制药资助,PROSPER在ClinicalTrials.gov注册号为NCT02003924)。





作者信息

Cora N. Sternberg, M.D., Karim Fizazi, M.D., Ph.D., Fred Saad, M.D., Neal D. Shore, M.D., Ugo De Giorgi, M.D., Ph.D., David F. Penson, M.D., M.P.H., Ubirajara Ferreira, M.D., Ph.D., Eleni Efstathiou, M.D., Ph.D., Katarzyna Madziarska, M.D., Ph.D., Michael P. Kolinsky, M.D., Daniel I. G. Cubero, M.D., Ph.D., Bettina Noerby, M.D., Fabian Zohren, M.D., Ph.D., Xun Lin, Ph.D., Katharina Modelska, M.D., Ph.D., Jennifer Sugg, M.S., Joyce Steinberg, M.D., and Maha Hussain, M.D. for the PROSPER Investigators*
From the Englander Institute for Precision Medicine, Weill Cornell Medicine, New York (C.N.S.); the University of Paris Saclay, Villejuif, France (K.F.); the University of Montreal Hospital Center, Montreal (F.S.), and Cross Cancer Institute, University of Alberta, Edmonton (M.P.K.) — both in Canada; the Carolina Urologic Research Center, Myrtle Beach, SC (N.D.S.); Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy (U.D.); Vanderbilt University, Nashville (D.F.P.); the State University of Campinas (Unicamp), Campinas (U.F.), and the ABC Foundation School of Medicine, Santo André (D.I.G.C.) — both in Brazil; M.D. Anderson Cancer Center, Houston (E.E.); Wroclaw Medical University, Wroclaw, Poland (K. Madziarska); Sygehus Lillebælt, Vejle, Denmark (B.N.); Pfizer, La Jolla (F.Z., X.L.), and Pfizer, San Francisco (K. Modelska) — both in California; and Astellas Pharma, Northbrook (J. Sugg, J. Steinberg), and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago (M.H.) — both in Illinois. Address reprint requests to Dr. Sternberg at Weill Cornell Medicine, Belfer Research Bldg., 413 E. 69th St., Rm. 1412, New York, NY 10021-5608, or at cns9006@med.cornell.edu. *A list of the PROSPER investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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