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转移性前列腺癌的恩杂鲁胺联合标准一线治疗
Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer


Ian D. Davis ... 肿瘤 • 2019.07.11
相关阅读
• 恩杂鲁胺治疗仅前列腺特异性抗原升高的去势抵抗性前列腺癌 • 转移性去势抵抗性前列腺癌的恩杂鲁胺耐药

摘要


背景

雄激素受体抑制剂恩杂鲁胺(enzalutamide)与去势抵抗性前列腺癌患者的总生存期改善相关。目前尚不明确在睾酮抑制(联合或不联合早期多西他赛治疗)的基础上加用恩杂鲁胺可否改善转移性激素敏感性前列腺癌患者的生存期。

 

方法

在这项开放标签、随机、3期试验中,我们分配患者接受睾酮抑制联合开放标签恩杂鲁胺治疗或联合标准非甾体类抗雄激素治疗(标准治疗组)。主要终点是总生存期。次要终点包括根据前列腺特异性抗原(PSA)水平确定的无进展生存期、临床无进展生存期和不良事件。

 

结果

共有1,125例患者接受随机分组;中位随访时间为34个月。恩杂鲁胺组和标准治疗组分别有102例和143例患者死亡(风险比,0.67;95%置信区间[CI],0.52~0.86;P=0.002)。在恩杂鲁胺组和标准治疗组中,3年总生存率的Kaplan-Meier估计值分别为80%(基于94起事件)和72%(基于130起事件)。在PSA无进展生存率(分别为174起事件和333起事件;风险比,0.39;P<0.001)和临床无进展生存率(分别为167起事件和320起事件;风险比,0.40;P<0.001)方面,恩杂鲁胺的结果也优于标准治疗。恩杂鲁胺组因不良事件而停止治疗的发生率高于标准治疗组(分别为33起事件和14起事件)。恩杂鲁胺组的疲劳发生率高于标准治疗组;恩杂鲁胺组有7例患者(1%)出现惊厥发作,标准治疗组无患者出现惊厥发作。

 

结论

在接受睾酮抑制的转移性激素敏感性前列腺癌患者中,恩杂鲁胺组的无进展生存期和总生存期均显著超过标准治疗组。恩杂鲁胺组的惊厥发作和其他毒性作用发生率高于标准治疗组,尤其是在接受早期多西他赛治疗的患者中(由Astellas Scientific and Medical Affairs等资助;ENZAMET(ANZUP 1304)在ANZCTR注册号为ACTRN12614000110684;在ClinicalTrials.gov注册号为NCT02446405;在欧盟临床试验注册系统[EU Clinical Trials Register]注册号为2014-003190-42)。





作者信息

Ian D. Davis, M.B., B.S., Ph.D., Andrew J. Martin, Ph.D., Martin R. Stockler, M.B., B.S., Stephen Begbie, M.B., B.S., Kim N. Chi, M.D., Simon Chowdhury, M.B., B.S., Ph.D., Xanthi Coskinas, M.Med.Sc., Mark Frydenberg, M.B., B.S., Wendy E. Hague, M.B., B.S., Ph.D., Lisa G. Horvath, M.B., B.S., Ph.D., Anthony M. Joshua, M.B., B.S., Ph.D., Nicola J. Lawrence, M.B., Ch.B., Gavin Marx, M.B., B.S., John McCaffrey, M.B., B.Ch., Ray McDermott, M.D., Ph.D., Margaret McJannett, R.N., Scott A. North, M.D., Francis Parnis, M.B., B.S., Wendy Parulekar, M.D., David W. Pook, M.B., B.S., M.D., M. Neil Reaume, M.D., Shahneen K. Sandhu, M.B., B.S., Alvin Tan, M.B., Ch.B., T. Hsiang Tan, M.B., B.S., Alastair Thomson, B.M., Emily Tu, Ph.D., Francisco Vera-Badillo, M.D., Scott G. Williams, M.B., B.S., M.D., Sonia Yip, Ph.D., Alison Y. Zhang, M.B., B.S., Robert R. Zielinski, M.B., B.S., and Christopher J. Sweeney, M.B., B.S. for the ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group*
From Monash University (I.D.D., M.F., D.W.P.), Eastern Health (I.D.D.), Australian Urology Associates (M.F.), Monash Health (D.W.P.), and the Peter MacCallum Cancer Centre and the University of Melbourne (S.K.S., S.G.W.), Melbourne, VIC, the National Health and Medical Research Council Clinical Trials Centre, University of Sydney (A.J.M., M.R.S., X.C., W.E.H., E.T., S.Y., A.Y.Z.), the Chris O’Brien Lifehouse (M.R.S., L.G.H., A.Y.Z.), the University of Sydney (L.G.H., G.M.), Royal Prince Alfred Hospital (L.G.H.), Kinghorn Cancer Centre, St. Vincent’s Hospital, and Garvan Institute of Medical Research (A.M.J.), Macquarie University (A.Y.Z.), and Western Sydney University (R.R.Z.), Sydney, Concord Cancer Centre, Concord Repatriation General Hospital, Concord, NSW (M.R.S.), Port Macquarie Base Hospital and Mid North Coast Cancer Institute Port Macquarie, Port Macquarie, NSW (S.B.), Sydney Adventist Hospital, Wahroonga, NSW (G.M.), the ANZUP Cancer Trials Group, Camperdown, NSW (M.M.), the Adelaide Cancer Centre and the University of Adelaide (F.P.) and the Royal Adelaide Hospital (T.H.T.), Adelaide, SA, and Orange Health Service, Central West Cancer Care Centre, Orange, NSW (R.R.Z.) — all in Australia; BC Cancer and the University of British Columbia, Vancouver (K.N.C.), the Cross Cancer Institute and the University of Alberta, Edmonton (S.A.N.), Canadian Cancer Trials Group, Queen’s University (W.P., F.V.-B.), and the Kingston Health Sciences Center (F.V.-B.), Kingston, ON, and the University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (M.N.R.) — all in Canada; Guy’s and St. Thomas’ NHS Foundation Trust Biomedical Research Centre, Cancer Research UK and King’s College London, and Sarah Cannon Research UK, London (S.C.), and the Royal Cornwall Hospital, Truro (A. Thomson) — all in the United Kingdom; Auckland City Hospital, Auckland (N.J.L.), and the Waikato District Health Board, Hamilton (A. Tan) — both in New Zealand; Cancer Trials Ireland (J.M., R.M.), Mater Misericordiae University Hospital (J.M.), and St. Vincent’s University Hospital and University College Dublin (R.M.D.) — all in Dublin; and Dana–Farber Cancer Institute and Harvard Medical School (C.J.S.) — both in Boston. Address reprint requests to Dr. Davis at Level 2, 5 Arnold St., Box Hill, VIC 3128, Australia, or at ian.davis@monash.edu. *A full list of the investigators in the ENZAMET Trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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