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肾细胞癌患者接受肾切除术后的帕博利珠单抗辅助治疗
Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma


Toni K. Choueiri ... 肿瘤 • 2021.08.19
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3期试验证实帕博利珠单抗肾癌术后辅助治疗显著改善无病生存期

 

李秦汉,范宇,张骞*

北京大学第一医院泌尿外科;北京大学泌尿外科研究所;国家泌尿、男性生殖系统研究中心

*通讯作者

 

肾癌是泌尿生殖系统的常见肿瘤之一,其中肾透明细胞癌占60%~85%。对于早期肾癌,标准治疗方式为肾部分切除术或者肾根治性切除术。然而手术之后,约一半患者面临肿瘤复发,其中大多数伴随远处转移1。肾透明细胞癌的TNM分期、核分级等危险因素与预后密切相关。同时,对于转移灶可切除的晚期肾癌,手术切除原发灶及转移灶也可能带来临床获益,但这些患者同样面临较高的术后复发风险。

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摘要


背景

对于肾切除术后的肾细胞癌患者,目前尚无旨在降低复发风险,且得到高水平证据支持的辅助治疗方案。

 

方法

在一项双盲3期试验中,我们以1∶1的比例将肾切除术后(行或未行转移灶切除术)复发风险高的肾透明细胞癌患者随机分组,两组分别接受每三周一次静脉给药的帕博利珠单抗(剂量为200 mg)辅助治疗或安慰剂,最多治疗17个周期(约1年)。主要终点是研究者判定的无病生存期。总生存期是关键次要终点。安全性是次要终点。

 

结果

共计496例患者被随机分配接受帕博利珠单抗治疗,498例患者被分配接受安慰剂治疗。在预设的期中分析中,从随机分组至数据截止日期的中位时间为24.1个月。帕博利珠单抗组的无病生存期显著超过安慰剂组(24个月时的无病生存率,77.3% vs. 68.1%;复发或死亡的风险比,0.68;95%置信区间[CI],0.53~0.87;P=0.002[双侧])。帕博利珠单抗组和安慰剂组在24个月时的估计生存率分别为96.6%和93.5%(死亡的风险比,0.54;95% CI,0.30~0.96)。帕博利珠单抗组和安慰剂组3级或更高级别不良事件(任何原因)的发生率分别为32.4%和17.7%。本试验未发生与帕博利珠单抗治疗相关的死亡。

 

结论

在复发风险高的肾癌患者中,与术后接受安慰剂治疗相比,帕博利珠单抗治疗显著延长了无病生存期(由默沙东[默克的子公司]资助,KEYNOTE-564在ClinicalTrials.gov注册号为NCT03142334)。





作者信息

Toni K. Choueiri, M.D., Piotr Tomczak, M.D., Ph.D., Se Hoon Park, M.D., Balaji Venugopal, M.D., Thomas Ferguson, M.D., Yen-Hwa Chang, M.D., Ph.D., Jaroslav Hajek, M.U.Dr., Stefan N. Symeonides, M.D., Ph.D., Jae Lyun Lee, M.D., Ph.D., Naveed Sarwar, M.D., Ph.D., Antoine Thiery-Vuillemin, M.D., Ph.D., Marine Gross-Goupil, M.D., Ph.D., Mauricio Mahave, M.D., Naomi B. Haas, M.D., Piotr Sawrycki, M.D., Howard Gurney, M.B., B.S., Christine Chevreau, M.D., Bohuslav Melichar, M.D., Ph.D., Evgeniy Kopyltsov, M.D., Ajjai Alva, M.D., John M. Burke, M.D., Gurjyot Doshi, M.D., Delphine Topart, M.D., Stephane Oudard, M.D., Ph.D., Hans Hammers, M.D., Ph.D., Hiroshi Kitamura, M.D., Ph.D., Jens Bedke, M.D., Rodolfo F. Perini, M.D., Pingye Zhang, Ph.D., Kentaro Imai, M.D., Jaqueline Willemann-Rogerio, M.D., David I. Quinn, M.D., Ph.D., and Thomas Powles, M.D. for the KEYNOTE-564 Investigators*
From Dana–Farber Cancer Institute, Boston (T.K.C.); Poznan University of Medical Sciences, Poznan (P.T.), and Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu, Torun (P.S.) — both in Poland; Sungkyunkwan University, Samsung Medical Center (S.H.P.), and Asan Medical Center, University of Ulsan College of Medicine (J.L.L.) — both in Seoul, South Korea; Beatson West of Scotland Cancer Centre and University of Glasgow, Glasgow (B.V.), Edinburgh Cancer Centre and University of Edinburgh, Edinburgh (S.N.S.), and Imperial College Healthcare NHS Trust (N.S.) and the Royal Free Hospital NHS Trust, University College London (T.P.), London — all in the United Kingdom; Fiona Stanley Hospital, Perth, WA (T.F.), and Macquarie University, Sydney (H.G.) — both in Australia; Taipei Veterans General Hospital, Taipei, Taiwan (Y.-H.C.); Fakultni Nemocnice Ostrava, Ostrava (J.H.), and Palacký University and University Hospital Olomouc, Olomouc (B.M.) — both in the Czech Republic; University Hospital Jean Minjoz, Besançon (A.T.-V.), University Hospital Bordeaux–Hôpital Saint-André, Bordeaux (M.G.-G.), Institut Universitaire du Cancer Toulouse–Oncopole, Toulouse (C.C.), Centre Hospitalier Universitaire de Montpellier, Montpellier (D.T.), and Hôpital Européen Georges Pompidou, University of Paris, Paris (S.O.) — all in France; Fundación Arturo López Pérez, Santiago, Chile (M.M.); Abramson Cancer Center, Philadelphia (N.H.); Omsk Clinical Oncology Dispensary, Omsk, Russia (E.K.); the University of Michigan, Ann Arbor (A.A.); Rocky Mountain Cancer Centers and U.S. Oncology Research, Denver (J.M.B.); Texas Oncology, U.S. Oncology Research, Woodlands (G.D.), and the University of Texas Southwestern, Dallas (H.H.); the University of Toyama, Toyama, Japan (H.K.); Eberhard Karls University Tübingen, Tübingen, Germany (J.B.); Merck, Kenilworth, NJ (R.F.P., P.Z., K.I., J.W.-R.); and USC Norris Comprehensive Cancer Center, Los Angeles (D.I.Q.). Address reprint requests to Dr. Choueiri at Dana–Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, or at toni_choueiri@dfci.harvard.edu. *A full list of the KEYNOTE-564 Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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