Phase III Study of Bevacizumab Plus Docetaxel Compared With Placebo Plus Docetaxel for the First-Line Treatment of Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer
Phase III Study of Bevacizumab Plus Docetaxel Compared With Placebo Plus Docetaxel for the First-Line Treatment of Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer
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DOI：
10.1200/jco.2008.21.6457
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发表时间：
2010-07-10
影响因子：
45.3
通讯作者：
Romieu, Gilles
中科院分区：
文献类型：
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作者：
Miles, David W.;Chan, Arlene;Romieu, Gilles
目的观察贝伐单抗联合化疗的疗效和安全性在一项三组、安慰剂对照的研究中，患者和方法患者（N = 736）被随机分配到多西他赛100 mg/m2+安慰剂或贝伐单抗7.5或15 mg/kg，每3周一次。主要终点是无进展生存期（PFS）;次要终点包括最佳总缓解、缓解持续时间、治疗失败时间、总生存期和安全性。结果在未分层分析中，贝伐单抗15 mg/kg（而非7.5 mg/kg）与多西他赛联合治疗的中位PFS（mPFS）优于安慰剂加多西他赛（安慰剂mPFS，8.2个月; 7.5 mg/kg mPFS，9.0个月[风险比（HR），0.86; P = .12]; 15 mg/kg mPFS，10.1个月[HR，0.77; P = .006]）和分层分析（安慰剂mPFS，8.1个月; 7.5 mg/kg mPFS，9.0个月[HR，0.80; P = .045]; 15 mg/kg mPFS，10.0个月[HR，0.67; P < .001]）。在基线时有可测量疾病的患者中，贝伐单抗15 mg/kg组的缓解率也增加（46% [安慰剂] vs 55% [7.5 mg/kg; P = 0.07]和64% [15 mg/kg; P <0.001]）。结论贝伐珠单抗联合多西他赛对多西他赛的安全性无明显影响。与多西他赛+安慰剂相比，贝伐珠单抗15 mg/kg每3周一次联合多西他赛作为MBC一线治疗可显著延长PFS。
Purpose The efficacy and safety of combining bevacizumab (7.5 and 15 mg/kg) with docetaxel as first-line therapy for human epidermal growth factor receptor 2 (HER2) -negative, locally recurrent or metastatic breast cancer (MBC) was investigated in a three-arm, placebo-controlled, phase III trial.Patients and Methods Patients (N = 736) were randomly assigned to docetaxel 100 mg/m(2) plus either placebo or bevacizumab 7.5 or 15 mg/kg every 3 weeks. The primary end point was progression-free survival (PFS); secondary end points included best overall response, duration of response, time to treatment failure, overall survival, and safety.Results Combination of bevacizumab 15 mg/kg, but not 7.5 mg/kg, with docetaxel showed superior median PFS (mPFS) to placebo plus docetaxel in unstratified analysis (placebo mPFS, 8.2 months; 7.5 mg/kg mPFS, 9.0 months [hazard ratio (HR), 0.86; P = .12]; 15 mg/kg mPFS, 10.1 months [HR, 0.77; P = .006]) and stratified analysis (placebo mPFS, 8.1 months; 7.5 mg/kg mPFS, 9.0 months [HR, 0.80; P = .045]; 15 mg/kg mPFS, 10.0 months [HR, 0.67; P < .001]). Response rates in patients with measurable disease at baseline also increased with bevacizumab 15 mg/kg (46% [placebo] v 55% [7.5 mg/kg; P = .07] and 64% [15 mg/kg; P < .001]). Combination with bevacizumab had limited impact on the known toxicity profile of docetaxel.Conclusion Combination of bevacizumab with docetaxel did not significantly impact on the safety profile of docetaxel. Bevacizumab 15 mg/kg every 3 weeks significantly increased PFS when combined with docetaxel as first-line therapy for MBC compared with docetaxel plus placebo.