Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer
Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer
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DOI：
10.1056/nejmoa1909707
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发表时间：
2019-12-19
影响因子：
158.5
通讯作者：
Bookman, M. A.
中科院分区：
文献类型：
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作者：
Coleman, R. L.;Fleming, G. F.;Bookman, M. A.
背景关于使用聚（腺苷二磷酸 [ADP]-核糖）聚合酶抑制剂（例如 veliparib）联合化疗，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 veliparib 添加到一线诱导的疗效 卡铂和紫杉醇化疗，并继续作为先前未经治疗的 III 期或 IV 期高级别浆液性卵巢癌患者的维持单药治疗。患者以 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整个 veliparib 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）和意向治疗人群中进行顺序分析。结果共有 1140 名患者接受了随机分组。在 BRCA 突变队列中，整个 veliparib 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，0.44；95% 置信区间 [CI]，0.28 至 0.68；P
BACKGROUNDData 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.METHODSIn 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.RESULTSA 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