BACKGROUND Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA-mutation cohort), and the intention-to-treat population. RESULTS A total of 1140 patients underwent randomization. In the BRCA-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall. CONCLUSIONS Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ClinicalTrials.gov number, NCT02470585.).

中文翻译：

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Veliparib 与一线化疗和卵巢癌维持治疗。


背景关于使用聚（腺苷二磷酸[ADP]-核糖）聚合酶抑制剂（例如veliparib）与化疗联合，然后维持作为高级别浆液性卵巢癌患者的初始治疗的数据有限。方法 在一项国际 3 期安慰剂对照试验中，我们评估了将 veliparib 添加到卡铂和紫杉醇一线诱导化疗中，并继续作为维持单一疗法治疗先前未经治疗的 III 期或 IV 期高级别浆液性卵巢癌患者的疗效。患者按 1:1:1 的比例随机分配接受化疗加安慰剂，然后安慰剂维持（对照），化疗加 veliparib，然后安慰剂维持（仅 veliparib 组合），或化疗加 veliparib，然后 veliparib 维持（整个 veliparib） 。细胞减灭术可以在试验治疗开始前或3个周期后进行。联合化疗为6个周期，维持治疗为另外30个周期。主要终点是研究者评估的 veliparib 整个治疗组与对照组相比的无进展生存期，在 BRCA 突变队列、同源重组缺陷 (HRD) 队列（包括 BRCA-突变队列）中进行顺序分析。突变队列）和意向治疗人群。结果 共有 1140 名患者接受了随机分组。在 BRCA 突变队列中，veliparib 治疗组的中位无进展生存期为 34.7 个月，对照组为 22.0 个月（进展或死亡的风险比为 0.44；95% 置信区间 [CI]，0.28 至 0.68） P<0.001);在 HRD 队列中，该时间分别为 31.9 个月和 20.5 个月（风险比，0。57； 95 CI，0.43 至 0.76； P<0.001);在意向治疗人群中，该时间为 23.5 个月和 17.3 个月（风险比，0.68；95% CI，0.56 至 0.83；P<0.001）。与化疗联合使用时，Veliparib 导致贫血和血小板减少症以及恶心和疲劳的发生率更高。结论 在所有试验人群中，卡铂、紫杉醇和 veliparib 诱导治疗方案以及 veliparib 维持治疗方案比单独卡铂加紫杉醇诱导治疗显着延长了无进展生存期。在诱导治疗期间添加 veliparib 而不维持 veliparib 的独立价值尚不明确。 （由艾伯维资助；VELIA/GOG-3005 ClinicalTrials.gov 编号，NCT02470585。）。