Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial
Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial
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DOI：
10.1200/jco.2013.51.4489
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发表时间：
2014-05-01
影响因子：
45.3
通讯作者：
Ray-Coquard, Isabelle
中科院分区：
文献类型：
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作者：
Pujade-Lauraine, Eric;Hilpert, Felix;Ray-Coquard, Isabelle
铂类耐药卵巢癌（OC）的标准化疗方案是单药化疗。贝伐珠单抗单药和联合用药均有活性。奥雷利亚是第一个随机III期试验，我们的知识相结合的贝伐单抗化疗铂耐药OC。患者和MethodsEligible患者有可测量/评估OC已进展< 6个月后完成铂为基础的治疗。患有难治性疾病、肠梗阻病史或既往接受过两次以上抗癌治疗的患者不合格。在研究者选择化疗（聚乙二醇脂质体多柔比星，每周紫杉醇或拓扑替康）后，患者被随机分配到单药化疗或贝伐珠单抗（10 mg/kg每2周一次或15 mg/kg每3周一次），直到进展，不可接受的毒性或撤回同意。在单独化疗进展后，允许交叉至单药贝伐珠单抗。主要终点是按RECIST评估的无进展生存期（PFS）。次要终点包括客观反应率（ORR），总生存期（OS），安全性和患者报告的outcomes.ResultsThe PFS风险比（HR）后，PFS事件在301 361例患者为0.48（95%CI，0.38至0.60;未分层的对数秩P <0.001）。单独化疗的中位PFS为3.4个月，而含贝伐珠单抗治疗的中位PFS为6.7个月。RECIST ORR分别为11.8%和27.3%（P = .001）。OS HR为0.85（95% CI，0.66至1.08; P <0.174;中位OS分别为13.3和16.6个月）。≥ 2级高血压和蛋白尿在贝伐单抗组更常见。胃肠道穿孔发生在2.2%的贝伐单抗治疗patients.Conclusionadding贝伐单抗化疗统计学显着改善PFS和ORR的OS趋势并不显着。未观察到新的安全性信号。
PurposeIn platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC.Patients and MethodsEligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes.ResultsThe PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade >= 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients.ConclusionAdding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.