Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial
Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial
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DOI：
10.1016/s1470-2045(14)70228-1
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发表时间：
2014-07-01
期刊：
影响因子：
51.1
通讯作者：
Matulonis, Ursula
中科院分区：
文献类型：
--
作者：
Ledermann, Jonathan;Harter, Philipp;Matulonis, Ursula
背景PARP抑制剂奥拉帕尼单药维持治疗与安慰剂相比显著延长了铂类药物敏感性复发性浆液性卵巢癌患者的无进展生存期（PFS）。我们的目的是探讨奥拉帕尼最有可能使BRCA突变患者受益的假设。方法我们提供了第二次总生存期中期分析的数据，以及我们随机、双盲、评估奥拉帕尼400 mg每日两次维持治疗的II期研究在接受过两种或两种以上铂类药物治疗方案且对最近的铂类药物治疗方案有部分或完全缓解的铂类药物敏感性复发性浆液性卵巢癌患者中比较（胶囊）与安慰剂。通过交互式语音应答系统进行随机化，根据倒数第二个铂类药物治疗方案的至进展时间、随机化前对最近一个铂类药物治疗方案的应答和种族血统进行分层。主要终点为PFS，分析总体人群和BRCA状态。该研究在ClinicalTrials.gov注册，编号NCT 00753545。结果在2008年8月28日至2010年2月9日期间，136名患者被分配到奥拉帕尼组，129名患者被分配到安慰剂组。奥拉帕尼组131例（96%）患者的BRCA状态已知，安慰剂组123例（95%）患者的BRCA状态已知，其中74例（56%）患者和62例（50%）患者存在有害或疑似有害的生殖系或肿瘤BRCA突变。在BRCA突变患者中，奥拉帕尼组的中位PFS显著长于安慰剂组（11.2个月[95%CI 8.3-无法计算] vs 4.3个月[3.0-5.4]; HR 0.18 [0.10-0.31]; p
Background Maintenance monotherapy with the PARP inhibitor olaparib significantly prolonged progression-free survival (PFS) versus placebo in patients with platinum-sensitive recurrent serous ovarian cancer. We aimed to explore the hypothesis that olaparib is most likely to benefit patients with a BRCA mutation.Methods We present data from the second interim analysis of overall survival and a retrospective, preplanned analysis of data by BRCA mutation status from our randomised, double-blind, phase 2 study that assessed maintenance treatment with olaparib 400 mg twice daily (capsules) versus placebo in patients with platinum-sensitive recurrent serous ovarian cancer who had received two or more platinum-based regimens and who had a partial or complete response to their most recent platinum-based regimen. Randomisation was by an interactive voice response system, stratified by time to progression on penultimate platinum-based regimen, response to the most recent platinum-based regimen before randomisation, and ethnic descent. The primary endpoint was PFS, analysed for the overall population and by BRCA status. This study is registered with ClinicalTrials.gov, number NCT00753545.Findings Between Aug 28, 2008, and Feb 9, 2010, 136 patients were assigned to olaparib and 129 to placebo. BRCA status was known for 131 (96%) patients in the olaparib group versus 123 (95%) in the placebo group, of whom 74 (56%) versus 62 (50%) had a deleterious or suspected deleterious germline or tumour BRCA mutation. Of patients with a BRCA mutation, median PFS was significantly longer in the olaparib group than in the placebo group (11.2 months [95% CI 8.3-not calculable] vs 4.3 months [3.0-5.4]; HR 0.18 [0.10-0.31]; p