BC Cancer Agency, Vancouver, Canada.
Lancet Oncol. 2011 Sep;12(9):852-61. doi: 10.1016/S1470-2045(11)70214-5. Epub 2011 Aug 19.
Olaparib (AZD2281) is a small-molecule, potent oral poly(ADP-ribose) polymerase (PARP) inhibitor. We aimed to assess the safety and tolerability of this drug in patients without BRCA1 or BRCA2 mutations with advanced triple-negative breast cancer or high-grade serous and/or undifferentiated ovarian cancer.
In this phase 2, multicentre, open-label, non-randomised study, women with advanced high-grade serous and/or undifferentiated ovarian carcinoma or triple-negative breast cancer were enrolled and received olaparib 400 mg twice a day. Patients were stratified according to whether they had a BRCA1 or BRCA2 mutation or not. The primary endpoint was objective response rate by Response Evaluation Criteria In Solid Tumors (RECIST). All patients who received treatment were included in the analysis of toxic effects, and patients who had measurable lesions at baseline were included in the primary efficacy analysis. This trial is registered at ClinicalTrials.gov, number NCT00679783.
91 patients were enrolled (65 with ovarian cancer and 26 breast cancer) and 90 were treated between July 8, 2008, and Sept 24, 2009. In the ovarian cancer cohorts, 64 patients received treatment. 63 patients had target lesions and therefore were evaluable for objective response as per RECIST. In these patients, confirmed objective responses were seen in seven (41%; 95% CI 22-64) of 17 patients with BRCA1 or BRCA2 mutations and 11 (24%; 14-38) of 46 without mutations. No confirmed objective responses were reported in patients with breast cancer. The most common adverse events were fatigue (45 [70%] of patients with ovarian cancer, 13 [50%] of patients with breast cancer), nausea (42 [66%] and 16 [62%]), vomiting (25 [39%] and nine [35%]), and decreased appetite (23 [36%] and seven [27%]).
Our study suggests that olaparib is a promising treatment for women with ovarian cancer and further assessment of the drug in clinical trials is needed.
AstraZeneca.
奥拉帕利（AZD2281）是一种小分子、强效的多聚（ADP-核糖）聚合酶（PARP）抑制剂。我们旨在评估该药在无 BRCA1 或 BRCA2 突变的晚期三阴性乳腺癌或高级别浆液性和/或未分化卵巢癌患者中的安全性和耐受性。
在这项 2 期、多中心、开放标签、非随机研究中，招募了晚期高级别浆液性和/或未分化卵巢癌或三阴性乳腺癌患者，并接受奥拉帕利 400mg，每日两次。患者根据是否存在 BRCA1 或 BRCA2 突变进行分层。主要终点是根据实体瘤反应评价标准（RECIST）评估的客观缓解率。所有接受治疗的患者均纳入毒性作用分析，基线时有可测量病变的患者纳入主要疗效分析。本试验在 ClinicalTrials.gov 注册，编号为 NCT00679783。
共纳入 91 例患者（65 例卵巢癌，26 例乳腺癌），90 例患者于 2008 年 7 月 8 日至 2009 年 9 月 24 日接受治疗。在卵巢癌队列中，64 例患者接受了治疗。63 例患者有靶病灶，因此可根据 RECIST 评估客观缓解。在这些患者中，17 例存在 BRCA1 或 BRCA2 突变的患者中有 7 例（41%；95%CI 22-64）和 46 例无突变的患者中有 11 例（24%；14-38）确认客观缓解。乳腺癌患者未报告确认的客观缓解。最常见的不良反应是疲劳（卵巢癌患者 45[70%]例，乳腺癌患者 13[50%]例）、恶心（42[66%]例和 16[62%]例）、呕吐（25[39%]例和 9[35%]例）和食欲下降（23[36%]例和 7[27%]例）。
我们的研究表明，奥拉帕利是一种有前途的治疗卵巢癌的药物，需要在临床试验中进一步评估该药物。
阿斯利康。
