奥拉帕利维持治疗铂敏感复发性卵巢癌。

Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer.

机构信息

University College London (UCL) Cancer Institute, UCL & UCL Hospitals Comprehensive Biomedical Research Centre, 90 Tottenham Court Rd., London W1T 4TJ, United Kingdom.

出版信息

N Engl J Med. 2012 Apr 12;366(15):1382-92. doi: 10.1056/NEJMoa1105535. Epub 2012 Mar 27.

DOI:10.1056/NEJMoa1105535

PMID:22452356

Abstract

BACKGROUND

Olaparib (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.

METHODS

We 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.

RESULTS

Of 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<0.001). Subgroup analyses of progression-free survival showed that, regardless of subgroup, patients in the olaparib group had a lower risk of progression. Adverse events more commonly reported in the olaparib group than in the placebo group (by more than 10% of patients) were nausea (68% vs. 35%), fatigue (49% vs. 38%), vomiting (32% vs. 14%), and anemia (17% vs. 5%); the majority of adverse events were grade 1 or 2. An interim analysis of overall survival (38% maturity, meaning that 38% of the patients had died) showed no significant difference between groups (hazard ratio with olaparib, 0.94; 95% CI, 0.63 to 1.39; P=0.75).

CONCLUSIONS

Olaparib as maintenance treatment significantly improved progression-free survival among patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. Interim analysis showed no overall survival benefit. The toxicity profile of olaparib in this population was consistent with that in previous studies. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT00753545.).

摘要

背景

奥拉帕利（AZD2281）是一种口服聚（二磷酸腺苷核糖）聚合酶抑制剂，在具有或不具有 BRCA1 或 BRCA2 种系突变的高级别浆液性卵巢癌患者中，具有抗肿瘤活性。

方法

我们进行了一项随机、双盲、安慰剂对照、2 期研究，以评估在接受过两种或更多种基于铂类的方案且对最近的基于铂类方案有部分或完全缓解的铂类敏感、复发的高级别浆液性卵巢癌患者中使用奥拉帕利进行维持治疗。患者被随机分配接受奥拉帕利，剂量为每日 400 毫克，每日两次，或安慰剂。主要终点是根据实体瘤反应评价标准评估的无进展生存期。

结果

在 265 名接受随机分组的患者中，136 名被分配到奥拉帕利组，129 名被分配到安慰剂组。与安慰剂相比，奥拉帕利组的无进展生存期显著延长（从化疗完成时随机分组开始的中位无进展生存期分别为 8.4 个月和 4.8 个月；进展或死亡的风险比为 0.35；95%置信区间[CI]为 0.25 至 0.49；P<0.001）。无进展生存期的亚组分析显示，无论亚组如何，奥拉帕利组的患者进展风险较低。与安慰剂组相比（超过 10%的患者），奥拉帕利组更常见的不良反应是恶心（68%比 35%）、疲劳（49%比 38%）、呕吐（32%比 14%）和贫血（17%比 5%）；大多数不良反应为 1 级或 2 级。总生存期的中期分析（成熟度为 38%，意味着 38%的患者死亡）显示两组之间无显著差异（奥拉帕利的风险比为 0.94；95%CI 为 0.63 至 1.39；P=0.75）。