Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.
Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.
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DOI：
10.1056/nejmoa1510016
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发表时间：
2015-11-05
期刊：
影响因子：
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通讯作者：
METEOR Investigators
中科院分区：
文献类型：
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作者：
Choueiri TK;Escudier B;Powles T;Mainwaring PN;Rini BI;Donskov F;Hammers H;Hutson TE;Lee JL;Peltola K;Roth BJ;Bjarnason GA;Géczi L;Keam B;Maroto P;Heng DY;Schmidinger M;Kantoff PW;Borgman-Hagey A;Hessel C;Scheffold C;Schwab GM;Tannir NM;Motzer RJ;METEOR Investigators
卡博替尼是一种口服小分子酪氨酸激酶抑制剂，靶向血管内皮生长因子受体（VEGFR）以及MET和AXL;每一种都涉及转移性肾细胞癌（RCC）病理生物学或对抗血管生成药物耐药性的发展。这项随机开放标签的3期试验评估了卡博替尼与依维莫司相比在VEGF靶向治疗后进展的RCC患者中的疗效。该试验随机分配了658名患者，每天接受60 mg剂量的卡博替尼或每天10 mg剂量的依维莫司。主要终点是无进展生存期。次要疗效终点为总生存期和客观缓解率。卡博替尼的中位无进展生存期为7.4个月，依维莫司为3.8个月。与依维莫司相比，卡博替尼的进展或死亡风险低42%（风险比，0.58; 95%置信区间[CI] 0.45至0.75; P < 0.001）。卡博替尼的客观缓解率为21%，依维莫司为5%（P < 0.001）。计划的中期分析显示，卡博替尼改善了总生存期（风险比，0.67; 95%CI，0.51至0.89; P = 0.005），但未越过显著性边界。74%的卡博替尼患者和65%的依维莫司患者报告了不良事件（3级或4级，无论因果关系如何）。9.1%的卡博替尼患者和10%的依维莫司患者因不良事件而停止研究治疗。与依维莫司相比，卡博替尼改善了在VEGF靶向治疗后进展的RCC患者的无进展生存期。
Cabozantinib is an oral small molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL; each has been implicated in metastatic renal cell carcinoma (RCC) pathobiology or development of resistance to antiangiogenic drugs. This randomized open-label phase 3 trial evaluated the efficacy of cabozantinib compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy. The trial randomized 658 patients to receive cabozantinib at a dose of 60 mg daily, or everolimus at a dose of 10 mg daily. The primary endpoint was progression-free survival. Secondary efficacy endpoints were overall survival and objective response rate. Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The risk of progression or death was 42% lower with cabozantinib compared to everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P < 0.001). Objective response rates were 21% with cabozantinib and 5% with everolimus (P < 0.001). A planned interim analysis showed that overall survival was improved with cabozantinib (hazard ratio, 0.67; 95% CI, 0.51 to 0.89; P = 0.005) but did not cross the significance boundary. Adverse events (grade 3 or 4, regardless of causality) were reported in 74% of cabozantinib patients and 65% of everolimus patients. Discontinuation of study treatment for adverse events occurred in 9.1% of cabozantinib patients and 10% of everolimus patients. Cabozantinib improved progression-free survival compared to everolimus in RCC patients who progressed after VEGFR-targeted therapy.