Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer
Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer
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DOI：
10.1056/nejmoa1105535
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发表时间：
2012-04-12
影响因子：
158.5
通讯作者：
Matulonis, Ursula
中科院分区：
文献类型：
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作者：
Ledermann, Jonathan;Harter, Philipp;Matulonis, Ursula
背景：AZD2281是一种口服多聚(二磷酸腺苷[ADP]-核糖)聚合酶抑制剂，在有或没有BRCA1或BRCA2胚系突变的高级别浆液性卵巢癌患者中显示出抗肿瘤活性。方法我们进行了一项随机、双盲、安慰剂对照的2期研究，以评估奥拉帕利对铂敏感、复发、高级别浆液性卵巢癌患者的维持治疗效果，这些患者接受了两种或两种以上以铂为基础的方案，并且对最近以铂为基础的方案有部分或完全反应。患者被随机分配接受奥拉帕利，每天两次，剂量为400毫克，或安慰剂。结果265名接受随机分组的患者中，136人被分配到奥拉帕利组，129人被分配到安慰剂组。奥拉帕利组的无进展生存期显著长于安慰剂组(化疗完成后随机分组的中位数分别为8.4个月和4.8个月；进展或死亡的风险比为0.35；95%可信区间[CI]，0.25至0.49；P
BACKGROUNDOlaparib (AZD2281) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that has shown antitumor activity in patients with high-grade serous ovarian cancer with or without BRCA1 or BRCA2 germline mutations.METHODSWe conducted a randomized, double-blind, placebo-controlled, phase 2 study to evaluate maintenance treatment with olaparib in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer who had received two or more platinum-based regimens and had had a partial or complete response to their most recent platinum-based regimen. Patients were randomly assigned to receive olaparib, at a dose of 400 mg twice daily, or placebo. The primary end point was progression-free survival according to the Response Evaluation Criteria in Solid Tumors guidelines.RESULTSOf 265 patients who underwent randomization, 136 were assigned to the olaparib group and 129 to the placebo group. Progression-free survival was significantly longer with olaparib than with placebo (median, 8.4 months vs. 4.8 months from randomization on completion of chemotherapy; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.25 to 0.49; P