Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
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DOI：
10.1056/nejmoa1910962
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发表时间：
2019-12-19
影响因子：
158.5
通讯作者：
Monk, B. J.
中科院分区：
文献类型：
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作者：
Gonzalez-Martin, A.;Pothuri, B.;Monk, B. J.
研究背景Niraparib是一种多聚腺苷二磷酸[ADP]-核糖聚合酶（PARP）抑制剂，无论是否存在BRCA突变，Niraparib均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。Niraparib在一线铂类化疗后有反应的新诊断晚期卵巢癌患者中的疗效尚不清楚。METHODS在这项随机、双盲、3期试验中，我们将新诊断晚期卵巢癌患者以2：1的比例随机分配至铂类化疗后有反应的患者接受Niraparib或安慰剂每日一次治疗。主要终点是同源重组缺陷肿瘤患者和总体人群的无进展生存期，由分层检验确定。在对无进展生存期进行初步分析时，对总生存期进行预先规定的中期分析。在733例接受随机分组的患者中，373例（50.9%）患有同源重组缺陷型肿瘤。在该类别的患者中，Niraparib组的中位无进展生存期显著长于安慰剂组（21.9个月vs. 10.4个月;疾病进展或死亡的风险比，0.43; 95%置信区间[CI]，0.31 - 0.59; P
BACKGROUNDNiraparib, 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 BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown.METHODSIn 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.RESULTSOf 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