The Royal Marsden National Health Service Foundation Trust and The Institute of Cancer Research, Sycamore House, Downs Rd, Sutton, Surrey SM2 5PT, UK.
J Clin Oncol. 2012 Feb 1;30(4):372-9. doi: 10.1200/JCO.2011.36.9215. Epub 2011 Dec 27.
Olaparib (AZD2281), an orally active poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in BRCA1- or BRCA2-deficient cells, has shown promising clinical efficacy in nonrandomized phase II trials in patients with ovarian cancer with BRCA1 or BRCA2 deficiency. We assessed the comparative efficacy and safety of olaparib and pegylated liposomal doxorubicin (PLD) in this patient population.
In this multicenter, open-label, randomized, phase II study, patients with ovarian cancer that recurred within 12 months of prior platinum therapy and with confirmed germline BRCA1 or BRCA2 mutations were enrolled. Patients were assigned in a 1:1:1 ratio to olaparib 200 mg twice per day or 400 mg twice per day continuously or PLD 50 mg/m(2) intravenously every 28 days. The primary efficacy end point was Response Evaluation Criteria in Solid Tumors (RECIST) -assessed progression-free survival (PFS). Secondary end points included objective response rate (ORR) and safety.
Ninety-seven patients were randomly assigned. Median PFS was 6.5 months (95% CI, 5.5 to 10.1 months), 8.8 months (95% CI, 5.4 to 9.2 months), and 7.1 months (95% CI, 3.7 to 10.7 months) for the olaparib 200 mg, olaparib 400 mg, and PLD groups, respectively. There was no statistically significant difference in PFS (hazard ratio, 0.88; 95% CI, 0.51 to 1.56; P = .66) for combined olaparib doses versus PLD. RECIST-assessed ORRs were 25%, 31%, and 18% for olaparib 200 mg, olaparib 400 mg, and PLD, respectively; differences were not statistically significant. Tolerability of both treatments was as expected based on previous trials.
The efficacy of olaparib was consistent with previous studies. However, the efficacy of PLD was greater than expected. Olaparib 400 mg twice per day is a suitable dose to explore in further studies in this patient population.
奥拉帕尼（AZD2281）是一种口服活性多聚（ADP-核糖）聚合酶抑制剂，可在 BRCA1 或 BRCA2 缺陷细胞中诱导合成致死，在 BRCA1 或 BRCA2 缺陷的卵巢癌患者的非随机 2 期临床试验中显示出有希望的临床疗效。我们评估了奥拉帕尼和聚乙二醇脂质体多柔比星（PLD）在这一患者人群中的疗效和安全性。
在这项多中心、开放性、随机、2 期研究中，纳入了在先前铂类治疗后 12 个月内复发且经证实存在种系 BRCA1 或 BRCA2 突变的卵巢癌患者。患者以 1:1:1 的比例随机分配至奥拉帕尼 200 mg，每日两次；或 400 mg，每日两次；或 PLD 50 mg/m2，每 28 天静脉注射一次。主要疗效终点为实体瘤反应评价标准（RECIST）评估的无进展生存期（PFS）。次要终点包括客观缓解率（ORR）和安全性。
97 例患者被随机分配。奥拉帕尼 200 mg、奥拉帕尼 400 mg 和 PLD 组的中位 PFS 分别为 6.5 个月（95%CI，5.5 至 10.1 个月）、8.8 个月（95%CI，5.4 至 9.2 个月）和 7.1 个月（95%CI，3.7 至 10.7 个月）。联合使用奥拉帕尼的剂量与 PLD 相比，PFS 无统计学显著差异（风险比，0.88；95%CI，0.51 至 1.56；P=0.66）。奥拉帕尼 200 mg、奥拉帕尼 400 mg 和 PLD 组的 RECIST 评估的 ORR 分别为 25%、31%和 18%；差异无统计学意义。两种治疗的耐受性与以前的试验一致。
奥拉帕尼的疗效与之前的研究一致。然而，PLD 的疗效大于预期。奥拉帕尼 400 mg，每日两次，是该患者人群进一步研究的合适剂量。
