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尼拉帕利治疗新诊断的晚期卵巢癌
Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer


Antonio González-Martín ... 肿瘤 妇产科和儿科 • 2019.12.19
NEJM 动画解读

PARP抑制剂治疗卵巢癌
相关阅读
• 奥拉帕利联合贝伐珠单抗作为卵巢癌的一线维持治疗 • 卵巢癌的维利帕利联合一线化疗和随后的维利帕利维持治疗 • 尼拉帕利用于铂类敏感型复发性卵巢癌的维持治疗

摘要


背景

在铂类化疗后的复发性卵巢癌患者中,多腺苷二磷酸核糖聚合酶(PARP)抑制剂尼拉帕利(niraparib)与无进展生存期显著延长相关,不论患者是否有BRCA突变。在新诊断出晚期卵巢癌,并且对一线铂类化疗产生应答的患者中,尼拉帕利的疗效尚未明确。

 

方法

在这项随机、双盲、3期试验中,我们以2∶1的比例将新诊断的晚期卵巢癌患者随机分组,两组分别在对铂类化疗产生应答后接受每日1次尼拉帕利或安慰剂治疗。主要终点是在患同源重组缺陷肿瘤的患者和总体人群中,通过分级检验确定的无进展生存期。在对无进展生存期进行主要分析时,我们对总生存期进行了预设的期中分析。

 

结果

在接受随机分组的733例患者中,373例(50.9%)患同源重组缺陷肿瘤。在这一类别的患者中,尼拉帕利组的中位无进展生存期显著超过安慰剂组(21.9个月 vs. 10.4个月;疾病进展或死亡的风险比,0.43;95%置信区间[CI],0.31~0.59;P<0.001)。在总体人群中,两组的相应无进展生存期分别为13.8个月和8.2个月(风险比,0.62;95% CI,0.50~0.76;P<0.001)。在24个月时的期中分析中,尼拉帕利组和安慰剂组的总生存率分别为84%和77%(风险比,0.70;95% CI,0.44~1.11)。最常见的3级或更高级别不良事件为贫血(31.0%的患者)、血小板减少症(28.7%)和中性粒细胞减少症(12.8%)。本试验未发生与治疗相关的死亡。

 

结论

在新诊断出晚期卵巢癌,并且对铂类化疗产生应答的患者中,无论是否有同源重组缺陷,尼拉帕利组的无进展生存期均显著超过安慰剂组(由葛兰素史克公司资助;PRIMA/ENGOT-OV26/GOG-3012在ClinicalTrials.gov注册号为NCT02655016)。





作者信息

Antonio González-Martín, M.D., Ph.D., Bhavana Pothuri, M.D., Ignace Vergote, M.D., Ph.D., René DePont Christensen, Ph.D., Whitney Graybill, M.D., Mansoor R. Mirza, M.D., Colleen McCormick, M.D., M.P.H., Domenica Lorusso, M.D., Ph.D., Paul Hoskins, M.D., Gilles Freyer, M.D., Klaus Baumann, M.D., Kris Jardon, M.D., Andrés Redondo, M.D., Ph.D., Richard G. Moore, M.D., Christof Vulsteke, M.D., Ph.D., Roisin E. O’Cearbhaill, M.D., Bente Lund, M.D., Floor Backes, M.D., Pilar Barretina-Ginesta, M.D., Ashley F. Haggerty, M.D., Maria J. Rubio-Pérez, M.D., Mark S. Shahin, M.D., Giorgia Mangili, M.D., William H. Bradley, M.D., Ilan Bruchim, M.D., Kaiming Sun, Ph.D., Izabela A. Malinowska, M.D., Ph.D., Yong Li, Ph.D., Divya Gupta, M.D., and Bradley J. Monk, M.D. for the PRIMA/ENGOT-OV26/GOG-3012 Investigators*
From Grupo Español de Investigación en Cáncer de Ovario (GEICO) and the Medical Oncology Department, Clínica Universidad de Navarra (A.G.-M.) and GEICO and Hospital Universitario La Paz-IdiPAZ (A.R.), Madrid, GEICO and Medical Oncology, Catalan Institute of Oncology, Girona Biomedical Research Institute, and the Department of Medical Sciences, Medical School University of Girona, Girona (P.B.-G.), and GEICO and Hospital Universitario Reina Sofía, Cordoba (M.J.R.-P.) — all in Spain; the Gynecologic Oncology Group (GOG) and the Department of Obstetrics/Gynecology, Perlmutter Cancer Center, NYU Langone Health (B.P.), and GOG and the Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College (R.E.O.), New York, and US Oncology Research (USOR) and the Division of Gynecologic Oncology, Wilmot Cancer Institute, Department of Obstetrics and Gynecology, University of Rochester, Rochester (R.G.M.) — all in New York; Belgium and Luxembourg Gynecologic Oncology Group (BGOG) and the Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven (I.V.), BGOG and the Department of Medical Oncology and Hematology, AZ Maria Middelares, Ghent (C.V.), and the Department of Molecular Imaging, Pathology, Radiotherapy, and Oncology, Center for Oncological Research, Antwerp University, Antwerp (C.V.) — all in Belgium; the Nordic Society of Gynecologic Oncology (NSGO) and the Research Unit of General Practice, Institute of Public Health, University of Southern Denmark, Odense (R.D.C.), NSGO and Rigshospitalet–Copenhagen University Hospital, Copenhagen (M.R.M.), and NSGO and the Department of Oncology, Aalborg University, Aalborg (B.L.) — all in Denmark; GOG and Gynecologic Oncology, Medical University of South Carolina, Charleston (W.G.); GOG and Legacy Medical Group Gynecologic Oncology, Portland, OR (C.M.); Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO) and Fondazione IRCCS National Cancer Institute of Milan (D.L.), and MITO and the Department of Obstetrics and Gynecology, San Raffaele Scientific Institute (G.M.) — both in Milan; USOR and the Department of Medical Oncology, BC Cancer, Vancouver, BC (P.H.), and GOG and the Department of Obstetrics and Gynecology, McGill University, and the Department of Oncology, McGill University Health Centre, Division of Gynecologic Oncology, Montreal (K.J.) — all in Canada; Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens and Service d’Oncologie Médicale, Centre Hospitalier Lyon-Sud, Lyon, France (G.F.); Arbeitsgemeinschaft Gynäkologische Onkologie and the Department of Gynecology and Obstetrics, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany (K.B.); the Division of Gynecologic Oncology, Ohio State University, Columbus (F.B.); GOG and the Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia (A.F.H.), and GOG and Hanjani Institute for Gynecologic Oncology, Asplundh Cancer Pavilion, Abington Jefferson Hospital, Sidney Kimmel Medical College of Thomas Jefferson University, Willow Grove (M.S.S.) — all in Pennsylvania; GOG and the Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee (W.H.B.); Israeli Society of Gynecologic Oncology and Department of Gynecology and Gynecologic Oncology, Hillel Yaffe Medical Center, Technion Israel Institute of Technology, Haifa, Israel (I.B.); GlaxoSmithKline/Tesaro, Waltham, MA (K.S., I.A.M., Y.L., D.G.); and Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix (B.J.M.). Address reprint requests to Dr. González-Martín at the Medical Oncology Department, Clínica Universidad de Navarra, Calle Marquesado de Santa Marta 1, Madrid 28027, Spain, or at agonzalezma@unav.es. *A complete list of investigators in the PRIMA/ENGOT-OV26/GOG-3012 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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