Sorafenib for Treatment of Renal Cell Carcinoma: Final Efficacy and Safety Results of the Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial
Sorafenib for Treatment of Renal Cell Carcinoma: Final Efficacy and Safety Results of the Phase III Treatment Approaches in Renal Cancer Global Evaluation Trial
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DOI：
10.1200/jco.2008.19.5511
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发表时间：
2009-07-10
影响因子：
45.3
通讯作者：
Bukowski, Ronald M.
中科院分区：
文献类型：
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作者：
Escudier, Bernard;Eisen, Tim;Bukowski, Ronald M.
PurposeMature生存数据和评估血管内皮生长因子（VEGF）作为一个预后生物标志物的治疗方法在肾癌全球评估试验（TARGET）研究肾细胞癌（RCC）的患者reported.Patients和MethodsNine百三个以前治疗的患者被随机分配到接受索拉非尼与安慰剂。在证明索拉非尼的无进展生存期（PFS）获益后，分配至安慰剂组的患者接受索拉非尼治疗。在两次计划的中期分析和一次最终分析中确定总生存期（OS），通过删失交叉至索拉非尼的安慰剂患者进行次要OS分析。基线VEGF水平与预后和疗效之间的关系进行了评估。结果接受索拉非尼治疗的患者的最终OS与接受安慰剂治疗的患者相当（分别为17.8和15.2个月;风险比[HR] = 0.88; P = 0.146）;然而，当交叉后安慰剂生存数据被删失时，差异变得显著（分别为17.8 v14.3个月; HR = 0.78; P = 0.029）。交叉后16个月的不良事件与先前报告的相似。基线VEGF水平与东部肿瘤协作组体力状态相关（P < .0001），纪念斯隆-凯特琳癌症中心评分（P < .0001），PFS和OS在单变量中（PFS，P = .0013; OS，P = .0009）和多变量（PFS，P = 0.0231; OS，P = 0.0416）安慰剂患者的分析和接受索拉非尼的患者的多变量分析的短OS（P = 0.0145）。高VEGF（P <0.01）和低VEGF（P <0.01）组均受益于索拉非尼。结论：尽管在主要意向治疗分析中未观察到OS获益，但对接受索拉非尼治疗的患者进行二次OS分析的结果显示，接受索拉非尼治疗的患者具有生存优势，这表明存在重要的交叉效应。VEGF水平是RCC患者PFS和OS的预后指标。TARGET的结果确立了索拉非尼在晚期RCC中的有效性和安全性。
PurposeMature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in patients with renal cell carcinoma (RCC) are reported.Patients and MethodsNine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated.ResultsThe final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio [HR] = 0.88; P = .146); however, when post-cross-over placebo survival data were censored, the difference became significant (17.8 v 14.3 months, respectively; HR = 0.78; P = .029). Adverse events at 16 months after cross over were similar to those previously reported. Baseline VEGF levels correlated with Eastern Cooperative Oncology Group performance status (P < .0001), Memorial Sloan-Kettering Cancer Center score (P < .0001), and PFS and OS in univariate (PFS, P = .0013; OS, P = .0009) and multivariate (PFS, P = .0231; OS, P = .0416) analyses of placebo patients and with short OS by multivariate analysis of patients receiving sorafenib (P = .0145). Both high-VEGF (P < .01) and low-VEGF (P < .01) groups benefited from sorafenib.ConclusionAlthough an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC.