尼拉帕利治疗新诊断的晚期卵巢癌患者。

Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.

机构信息

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.).

出版信息

N Engl J Med. 2019 Dec 19;381(25):2391-2402. doi: 10.1056/NEJMoa1910962. Epub 2019 Sep 28.

DOI:10.1056/NEJMoa1910962

PMID:31562799

Abstract

BACKGROUND

Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown.

METHODS

In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival.

RESULTS

Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred.

CONCLUSIONS

Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).

摘要

背景

尼拉帕利是一种聚（二腺苷二磷酸核糖）聚合酶（PARP）抑制剂，与铂类化疗后复发性卵巢癌患者的无进展生存期显著增加相关，无论是否存在突变。在一线铂类化疗后有反应的新诊断晚期卵巢癌患者中，尼拉帕利的疗效尚不清楚。

方法

在这项随机、双盲、3 期临床试验中，我们以 2:1 的比例随机分配新诊断的晚期卵巢癌患者，在铂类化疗后有反应的情况下，每天接受尼拉帕利或安慰剂治疗。主要终点是同源重组缺陷患者和总体人群的无进展生存期，这是在分层检验中确定的。在无进展生存的主要分析时，进行了总体生存的预先指定的中期分析。

结果

在 733 名接受随机分组的患者中，有 373 名（50.9%）肿瘤存在同源重组缺陷。在这一类别中，尼拉帕利组的中位无进展生存期明显长于安慰剂组（21.9 个月 vs. 10.4 个月；疾病进展或死亡的风险比为 0.43；95%置信区间 [CI]，0.31 至 0.59；P<0.001）。在总体人群中，相应的无进展生存期为 13.8 个月和 8.2 个月（风险比为 0.62；95%CI，0.50 至 0.76；P<0.001）。在 24 个月的中期分析中，尼拉帕利组的总生存率为 84%，安慰剂组为 77%（风险比为 0.70；95%CI，0.44 至 1.11）。最常见的 3 级或以上不良事件为贫血（31.0%的患者）、血小板减少（28.7%）和中性粒细胞减少（12.8%）。没有与治疗相关的死亡事件发生。