BACKGROUND Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation. (Funded by ARCAGY Research and others; PAOLA-1 ClinicalTrials.gov number, NCT02477644.).

中文翻译：

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奥拉帕利加贝伐单抗作为卵巢癌的一线维持治疗。

背景技术奥拉帕里布已经显示出在具有新诊断的患有BRCA突变的晚期卵巢癌的妇女中作为维持治疗的显着临床益处。不管BRCA突变状态如何，维持奥拉帕尼和贝伐单抗联合治疗对患者的作用尚不清楚。方法我们进行了一项随机，双盲，国际3期试验。符合条件的患者具有新诊断，晚期，高度卵巢癌，在一线铂-紫杉烷化疗加贝伐单抗后反应良好。无论手术结局或BRCA突变状态如何，患者均符合条件。患者按照2：1的比例随机分配，以接受olaparib片（300 mg每天两次）或安慰剂长达24个月。所有患者每3周接受一次贝伐单抗，剂量为每公斤体重15毫克，共15个月。主要终点是从随机分组到研究者评估的疾病进展或死亡的时间。结果在806例接受随机分组的患者中，有537例被分配接受奥拉帕尼治疗，269例被接受安慰剂治疗。中位随访22.9个月后，奥拉帕尼+贝伐单抗的中位无进展生存期为22.1个月，而安慰剂+贝伐单抗的中位无进展生存期为16.6个月（疾病进展或死亡的危险比，0.59； 95％置信区间[CI]，0.49）至0.72； P <0.001）。同源重组缺乏症（HRD）阳性的患者（包括具有BRCA突变（中位进展）的肿瘤），疾病进展或死亡的风险比（奥拉帕尼组与安慰剂组）为0.33（95％CI，0.25至0.45）无生存期，分别为37.2和17.7个月）和0.43（95％CI，0.28至0）。66）没有BRCA突变的HRD阳性肿瘤患者（中位无进展生存期，28.1 vs. 16.6个月）。不良事件与奥拉帕尼和贝伐单抗的既定安全性一致。结论在接受包括贝伐单抗在内的一线标准疗法的晚期卵巢癌患者中，添加奥拉帕尼维持治疗可提供显着的无进展生存获益，这对于HRD阳性肿瘤患者（包括未发生BRCA突变的患者）是非常重要的。（由ARCAGY Research和其他机构资助； PAOLA-1 ClinicalTrials.gov编号，NCT02477644。）。结论在接受包括贝伐单抗在内的一线标准疗法的晚期卵巢癌患者中，添加奥拉帕尼维持治疗可提供显着的无进展生存获益，这对于HRD阳性肿瘤患者（包括未发生BRCA突变的患者）是非常重要的。（由ARCAGY Research和其他机构资助； PAOLA-1 ClinicalTrials.gov编号，NCT02477644。）。结论在接受包括贝伐单抗在内的一线标准疗法的晚期卵巢癌患者中，添加奥拉帕尼维持治疗可提供显着的无进展生存获益，这对于HRD阳性肿瘤患者（包括未发生BRCA突变的患者）是非常重要的。（由ARCAGY Research和其他机构资助； PAOLA-1 ClinicalTrials.gov编号，NCT02477644。）。