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阿维鲁单抗和阿昔替尼联合疗法与舒尼替尼治疗晚期肾细胞癌的比较
Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma


Robert J. Motzer ... 肿瘤 • 2019.03.21
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晚期肾癌患者新希望:免疫检查点抑制剂联合靶向药一线治疗

 

李泓

嘉会国际医院肿瘤中心

 

肾透明细胞癌(RCC)是泌尿系统常见的恶性肿瘤。很多RCC患者在病程中长时间无临床症状,导致首诊时RCC已局部进展或转移而无法行根治性手术。此外,也有许多患者术后出现复发。因此全身治疗在此类患者治疗中发挥重要作用。

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摘要


背景

在一项单组、1b期试验中,阿维鲁单抗(avelumab)联合阿昔替尼使晚期肾细胞癌患者达到客观缓解。在既往未接受过治疗的晚期肾细胞癌患者中进行的这项3期试验对阿维鲁单抗联合阿昔替尼治疗与标准舒尼替尼治疗进行了比较。

 

方法

我们以1∶1的比例将患者随机分组,分别接受每2周1次阿维鲁单抗(每次10 mg/kg体重)静脉给药+每日2次阿昔替尼(每次5 mg)口服给药或者每日1次舒尼替尼(50 mg)口服给药,舒尼替尼每6周一个周期,每个周期用药4周。两个独立主要终点分别为程序性死亡蛋白配体-1(PD-L1)阳性肿瘤患者的无进展生存期和总生存期。一个关键次要终点是整体人群的无进展生存期;其他终点包括客观缓解和安全性。

 

结果

共有886例患者被分配接受阿维鲁单抗+阿昔替尼(442例患者)或舒尼替尼(444例患者)治疗。在560例PD-L1阳性肿瘤患者(63.2%)中,阿维鲁单抗+阿昔替尼组和舒尼替尼组的中位无进展生存期分别为13.8个月和7.2个月(疾病进展或死亡的风险比,0.61;95%置信区间[CI],0.47~0.79;P<0.001);在整体人群中,中位无进展生存期分别为13.8个月和8.4个月(风险比,0.69;95% CI,0.56~0.84;P<0.001)。在PD-L1阳性肿瘤患者中,阿维鲁单抗+阿昔替尼组和舒尼替尼组的客观缓解率分别为55.2%和25.5%;两组总生存期的中位随访时间分别为11.6个月和10.7个月,当时分别有37例患者和44例患者已死亡。阿维鲁单抗+阿昔替尼组99.5%的患者和舒尼替尼组99.3%的患者在治疗期间发生了不良事件;分别有71.2%和71.5%的患者发生了3级或更高级别的不良事件。

 

结论

在接受阿维鲁单抗+阿昔替尼和舒尼替尼一线治疗的晚期肾细胞癌患者中,前者的无进展生存期显著超过后者(由辉瑞和默克[德国达姆施塔特]资助;JAVELIN Renal 101在ClinicalTrials.gov注册号为NCT02684006)。





作者信息

Robert J. Motzer, M.D., Konstantin Penkov, M.D., Ph.D., John Haanen, Ph.D., Brian Rini, M.D., Laurence Albiges, M.D., Ph.D., Matthew T. Campbell, M.D., Balaji Venugopal, M.D., Christian Kollmannsberger, M.D., Sylvie Negrier, M.D., Ph.D., Motohide Uemura, M.D., Ph.D., Jae L. Lee, M.D., Ph.D., Aleksandr Vasiliev, M.D., Wilson H. Miller, Jr., M.D., Ph.D., Howard Gurney, M.D., Manuela Schmidinger, M.D., James Larkin, M.D., Ph.D., Michael B. Atkins, M.D., Jens Bedke, M.D., Boris Alekseev, M.D., Jing Wang, Ph.D., Mariangela Mariani, Ph.D., Paul B. Robbins, Ph.D., Aleksander Chudnovsky, M.D., Camilla Fowst, M.D., Subramanian Hariharan, M.D., Bo Huang, Ph.D., Alessandra di Pietro, M.D., Ph.D., and Toni K. Choueiri, M.D.
From Memorial Sloan Kettering Cancer Center (R.J.M.) and Pfizer (S.H.), New York; Private Medical Institution Euromedservice (K.P.) and Nonstate Health Institution Road Clinical Hospital–Russian Railways (A.V.), St. Petersburg, and the Moscow Scientific Research Oncology Institute, Moscow (B.A.) — all in Russia; the Netherlands Cancer Institute, Amsterdam (J.H.); the Cleveland Clinic, Cleveland (B.R.); Institut Gustave Roussy, Villejuif (L.A.), and Centre Léon Bérard, University of Lyon, Lyon (S.N.) — both in France; the University of Texas M.D. Anderson Cancer Center, Houston (M.T.C.); University of Glasgow, Beatson West of Scotland Cancer Centre, Glasgow (B.V.), and Royal Marsden NHS Foundation Trust, London (J.L.) — both in the United Kingdom; British Columbia Cancer Agency, Vancouver (C.K.), and Lady Davis Institute and Jewish General Hospital, McGill University, Montreal (W.H.M.) — both in Canada; Osaka University Hospital, Osaka, Japan (M.U.); University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea (J.L.L.); Macquarie University, Sydney (H.G.); Department of Medicine I, Clinical Division of Oncology and Comprehensive Cancer Center, Medical University of Vienna, Vienna (M.S.); Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (M.B.A.); Department of Urology, University of Tübingen, Tübingen, Germany (J.B.); Pfizer, Cambridge (J.W., A.C.), and the Lank Center for Genitourinary Oncology at Dana–Farber Cancer Institute, and Brigham and Women’s Hospital, Boston (T.K.C.) — both in Massachusetts; Pfizer (M.M., A.P.) and Pfizer Italia (C.F.), Milan; Pfizer, San Diego, CA (P.B.R.); and Pfizer, Groton, CT (B.H.). Address reprint requests to Dr. Motzer at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, or at motzerr@mskcc.org; or to Dr. Choueiri at Dana–Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, or at toni_choueiri@dfci.harvard.edu.

 

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