Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy
Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy
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DOI：
10.1056/nejmoa1611406
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发表时间：
2016-12-08
影响因子：
158.5
通讯作者：
Patard, J. -J.
中科院分区：
文献类型：
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作者：
Ravaud, A.;Motzer, R. J.;Patard, J. -J.
背景舒尼替尼是一种血管内皮生长因子途径抑制剂，是治疗转移性肾细胞癌的有效方法。我们试图确定舒尼替尼对肾切除术后肿瘤复发高风险的局部区域肾细胞癌患者的疗效和安全性。 方法 在这项随机、双盲、3 期试验中，我们分配 615 名局部区域高风险透明细胞肾细胞癌患者接受舒尼替尼（每天 50 毫克）或安慰剂治疗，为期 1 年，疗程为 4 周，停药 2 周。复发、不可接受的毒性或撤回同意。根据盲法独立中央审查，主要终点是无病生存期。次要终点包括研究者评估的无病生存期、总生存期和安全性。 结果 舒尼替尼组的中位无病生存期为 6.8 年（95% 置信区间 [CI]，5.8 至未达到），安慰剂组为 5.6 年（95% CI，3.8 至 6.6）（风险比，0.76；95% CI，0.59 至未达到）。 0.98；P = 0.03）。数据截止时总体生存数据尚未成熟。舒尼替尼组因不良事件而减少剂量的频率高于安慰剂组（34.3% vs. 2%），剂量中断（46.4% vs. 13.2%）和停药（28.1% vs. 5.6%）也是如此。舒尼替尼组中 3 级或 4 级不良事件的发生率（3 级事件为 48.4%，4 级事件为 12.1%）比安慰剂组（分别为 15.8% 和 3.6%）更常见。两组严重不良事件的发生率相似（舒尼替尼组为 21.9%，安慰剂组为 17.1%）；没有死亡归因于毒性作用。 结论 在肾切除术后肿瘤复发高风险的局部透明细胞肾细胞癌患者中，舒尼替尼组的中位无病生存期显着长于安慰剂组，但代价是毒性事件发生率更高。 （由辉瑞资助；S-TRAC ClinicalTrials.gov 编号，NCT00375674。）
BACKGROUND Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy.METHODS In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety.RESULTS The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P = 0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects.CONCLUSIONS Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials. gov number, NCT00375674.)