Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial
Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial
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DOI：
10.1200/jco.2009.23.9764
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发表时间：
2010-02-20
影响因子：
45.3
通讯作者：
Hawkins, Robert E.
中科院分区：
文献类型：
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作者：
Sternberg, Cora N.;Davis, Ian D.;Hawkins, Robert E.
目的帕唑帕尼是一种以血管内皮生长因子受体、血小板衍生生长因子受体和c-Kit为靶点的口服血管生成抑制剂。本随机，双盲，安慰剂对照的III期研究评估了帕唑帕尼单药治疗的疗效和安全性，在治疗初治和长春新碱预处理的晚期肾细胞癌（RCC）患者和MethodsAdult患者可测量的，局部晚期，和/或转移性RCC随机分配2：1接受口服帕唑帕尼或安慰剂。主要终点是无进展生存期（PFS）。次要终点包括总生存期、肿瘤缓解率（实体瘤缓解评价标准）和安全性。肿瘤的放射学评估进行了独立review.ResultsOf 435例患者入组，233是治疗幼稚（54%）和202细胞因子预处理（46%）。在整个研究人群中，与安慰剂相比，帕唑帕尼显著延长了PFS（中位数，PFS 9.2 vs 4.2个月;风险比[HR]，0.46; 95%CI，0.34 - 0.62; P <0.0001），初治亚群（中位PFS 11.1 v2.8个月; HR，0.40; 95%CI，0.27至0.60; P < .0001），以及曲马多碱预治疗亚群（中位PFS，7.4 v4.2个月; HR，0.54; 95%CI，0.35至0.84; P < .001）。帕唑帕尼组的客观反应率为30%，安慰剂组为3%（P <0.001）。中位缓解持续时间超过1年。最常见的不良反应是腹泻、高血压、毛发颜色改变、恶心、厌食和呕吐。没有证据表明pazopanib与placebo.Conclusionpazopanib的生活质量的临床重要差异表现出显着的改善PFS和肿瘤反应与安慰剂相比，在治疗初治和长春碱预处理的晚期和/或转移性RCC患者。J Clin Oncol 28：1061-1068. (C)2010年美国临床肿瘤学会
PurposePazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit. This randomized, double-blind, placebo-controlled phase III study evaluated efficacy and safety of pazopanib monotherapy in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC).Patients and MethodsAdult patients with measurable, locally advanced, and/or metastatic RCC were randomly assigned 2: 1 to receive oral pazopanib or placebo. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response rate (Response Evaluation Criteria in Solid Tumors), and safety. Radiographic assessments of tumors were independently reviewed.ResultsOf 435 patients enrolled, 233 were treatment naive (54%) and 202 were cytokine pretreated (46%). PFS was significantly prolonged with pazopanib compared with placebo in the overall study population (median, PFS 9.2 v 4.2 months; hazard ratio [HR], 0.46; 95% CI, 0.34 to 0.62; P < .0001), the treatment-naive subpopulation (median PFS 11.1 v 2.8 months; HR, 0.40; 95% CI, 0.27 to 0.60; P < .0001), and the cytokine-pretreated subpopulation (median PFS, 7.4 v 4.2 months; HR, 0.54; 95% CI, 0.35 to 0.84; P < .001). The objective response rate was 30% with pazopanib compared with 3% with placebo (P < .001). The median duration of response was longer than 1 year. The most common adverse events were diarrhea, hypertension, hair color changes, nausea, anorexia, and vomiting. There was no evidence of clinically important differences in quality of life for pazopanib versus placebo.ConclusionPazopanib demonstrated significant improvement in PFS and tumor response compared with placebo in treatment-naive and cytokine-pretreated patients with advanced and/or metastatic RCC. J Clin Oncol 28: 1061-1068. (C) 2010 by American Society of Clinical Oncology