Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer
Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer
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DOI：
10.1056/nejmoa1104390
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发表时间：
2011-12-29
影响因子：
158.5
通讯作者：
Liang, Sharon X.
中科院分区：
文献类型：
--
作者：
Burger, Robert A.;Brady, Mark F.;Liang, Sharon X.
血管内皮生长因子是上皮性卵巢癌血管生成和疾病进展的关键促进因子。贝伐单抗是一种人源化抗血管内皮生长因子单克隆抗体，在复发性肿瘤女性中显示出单药活性。因此，我们的目的是评估除了贝伐单抗的标准一线therapy.METHODSIn我们的双盲，安慰剂对照，3期试验，我们随机分配符合条件的新诊断的III期（不完全切除）或IV期上皮性卵巢癌谁经历了减瘤手术接受三种治疗之一。所有三种药物均包括化疗，包括静脉注射紫杉醇，剂量为175 mg/m2体表面积，加卡铂，曲线下面积为6，第1至6个周期，加上第2至22个周期的研究治疗，每个周期3周。对照治疗是在第2至22周期添加安慰剂的化疗;贝伐珠单抗起始治疗是在第2至6周期添加贝伐珠单抗（15 mg/公斤体重）的化疗，并在第7至22周期添加安慰剂。贝伐珠单抗-整个治疗是化疗，在第2至22周期添加贝伐珠单抗。主要终点是无进展生存期。总共有1873名妇女参加。对照组的中位无进展生存期为10.3个月，贝伐珠单抗起始组为11.2个月，贝伐珠单抗全程组为14.1个月。相对于对照治疗，贝伐单抗治疗组进展或死亡的风险比为0.908（95%置信区间[CI]，0.795至1.040; P=0.16），贝伐单抗治疗组为0.717（95% CI，0.625至0.824; P = 0.16）。
BACKGROUNDVascular endothelial growth factor is a key promoter of angiogenesis and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, has shown single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate the addition of bevacizumab to standard front-line therapy.METHODSIn our double-blind, placebo-controlled, phase 3 trial, we randomly assigned eligible patients with newly diagnosed stage III (incompletely resectable) or stage IV epithelial ovarian cancer who had undergone debulking surgery to receive one of three treatments. All three included chemotherapy consisting of intravenous paclitaxel at a dose of 175 mg per square meter of body-surface area, plus carboplatin at an area under the curve of 6, for cycles 1 through 6, plus a study treatment for cycles 2 through 22, each cycle of 3 weeks' duration. The control treatment was chemotherapy with placebo added in cycles 2 through 22; bevacizumab-initiation treatment was chemotherapy with bevacizumab (15 mg per kilogram of body weight) added in cycles 2 through 6 and placebo added in cycles 7 through 22. Bevacizumab-throughout treatment was chemotherapy with bevacizumab added in cycles 2 through 22. The primary end point was progression-free survival.RESULTSOverall, 1873 women were enrolled. The median progression-free survival was 10.3 months in the control group, 11.2 in the bevacizumab-initiation group, and 14.1 in the bevacizumab-throughout group. Relative to control treatment, the hazard ratio for progression or death was 0.908 (95% confidence interval [CI], 0.795 to 1.040; P=0.16) with bevacizumab initiation and 0.717 (95% CI, 0.625 to 0.824; P