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阿帕鲁胺治疗转移性去势敏感性前列腺癌
Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer


Kim N. Chi ... 肿瘤 • 2019.07.04
相关阅读
• 转移性前列腺癌

摘要


背景

阿帕鲁胺(apalutamide)是雄激素受体的配体结合域抑制剂。目前尚未明确在转移性去势敏感性前列腺癌患者中,与雄激素剥夺治疗(ADT)加用安慰剂相比,ADT加用阿帕鲁胺可否延长患者的影像学无进展生存期和总生存期。

 

方法

在这项双盲、3期试验中,我们将转移性去势敏感性前列腺癌患者随机分组,分别在ADT的基础上加用阿帕鲁胺(每日240 mg)或安慰剂。本试验允许患者接受过针对局限性疾病的治疗和多西他赛治疗。主要终点是影像学无进展生存期和总生存期。

 

结果

共有525例患者被分配接受阿帕鲁胺+ADT治疗,527例患者被分配接受安慰剂+ADT治疗。患者中位年龄为68岁。共有16.4%的患者接受过前列腺切除术或局限性疾病放疗,10.7%接受过多西他赛治疗;62.7%患高容量疾病,37.3%患低容量疾病。在中位随访时间为22.7个月的第一次期中分析时,阿帕鲁胺组和安慰剂组的24个月影像学无进展生存率分别为68.2%和47.5%(影像学进展或死亡的风险比,0.48;95%置信区间[CI],0.39~0.60;P<0.001)。阿帕鲁胺组的24个月总生存率也高于安慰剂组(阿帕鲁胺组82.4% vs.安慰剂组73.5%;死亡的风险比,0.67;95% CI,0.51~0.89;P=0.005)。阿帕鲁胺组和安慰剂组的3或4级不良事件发生率分别为42.2%和40.8%,阿帕鲁胺组的皮疹发生率高于安慰剂组。

 

结论

在这项纳入转移性去势敏感性前列腺癌患者的试验中,ADT+阿帕鲁胺组的总生存期和影像学无进展生存期均显著超过ADT+安慰剂组,且两组的副作用无显著差异(由Janssen Research and Development资助;TITAN在ClinicalTrials.gov注册号为NCT02489318)。





作者信息

Kim N. Chi, M.D., Neeraj Agarwal, M.D., Anders Bjartell, M.D., Byung Ha Chung, M.D., Andrea J. Pereira de Santana Gomes, M.D., Robert Given, M.D., Álvaro Juárez Soto, M.D., Axel S. Merseburger, M.D., Mustafa Özgüroğlu, M.D., Hirotsugu Uemura, M.D., Dingwei Ye, M.D., Kris Deprince, M.D., Vahid Naini, Pharm.D., Jinhui Li, Ph.D., Shinta Cheng, M.D., Margaret K. Yu, M.D., Ke Zhang, Ph.D., Julie S. Larsen, Pharm.D., Sharon McCarthy, B.Pharm., and Simon Chowdhury, M.D. for the TITAN Investigators*
From BC Cancer and Vancouver Prostate Centre, Vancouver, Canada (K.N.C.); Huntsman Cancer Institute, University of Utah, Salt Lake City (N.A.); Skåne University Hospital, Lund University, Malmö, Sweden (A.B.); Yonsei University College of Medicine and Gangnam Severance Hospital, Seoul, South Korea (B.H.C.); Liga Norte Riograndense Contra o Câncer, Natal, Brazil (A.J.P.S.G.); Urology of Virginia, Eastern Virginia Medical School, Norfolk (R.G.); Hospital Universitario de Jerez de la Frontera, Cadiz, Spain (A.J.S.); University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany (A.S.M.); Istanbul University–Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey (M.O.); Kindai University Hospital Faculty of Medicine, Osaka, Japan (H.U.); Fudan University Shanghai Cancer Center, Shanghai, China (D.Y.); Janssen Research and Development, Beerse, Belgium (K.D.); Janssen Research and Development, San Diego (V.N., J.L., K.Z.), and Janssen Research and Development, Los Angeles (M.K.Y., J.S.L.) — both in California; Janssen Research and Development, Raritan, NJ (S. Cheng, S.M.); and Guy’s, King’s, and St. Thomas’ Hospitals and the Sarah Cannon Research Institute, London (S. Chowdhury). Address reprint requests to Dr. Chi at BC Cancer and Vancouver Prostate Centre, Vancouver Centre, 600 W. 10th Ave., Vancouver, BC V5Z 1L3, Canada, or at kchi@bccancer.bc.ca. *A complete list of investigators in the TITAN trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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