舒尼替尼与干扰素α治疗转移性肾细胞癌患者的总生存期及更新结果比较
Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma.
作者信息
Motzer Robert J, Hutson Thomas E, Tomczak Piotr, Michaelson M Dror, Bukowski Ronald M, Oudard Stéphane, Negrier Sylvie, Szczylik Cezary, Pili Roberto, Bjarnason Georg A, Garcia-del-Muro Xavier, Sosman Jeffrey A, Solska Ewa, Wilding George, Thompson John A, Kim Sindy T, Chen Isan, Huang Xin, Figlin Robert A
机构信息
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
出版信息
J Clin Oncol. 2009 Aug 1;27(22):3584-90. doi: 10.1200/JCO.2008.20.1293. Epub 2009 Jun 1.
PURPOSE
A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-alpha) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported.
PATIENTS AND METHODS
Seven hundred fifty treatment-naïve patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-alpha 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up.
RESULTS
Median overall survival was greater in the sunitinib group than in the IFN-alpha group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR was 0.818 (95% CI, 0.669 to 0.999; P = .049). Within the IFN-alpha group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor-signaling inhibitors after discontinuation from the trial. Median progression-free survival was 11 months for sunitinib compared with 5 months for IFN-alpha (P < .001). Objective response rate was 47% for sunitinib compared with 12% for IFN-alpha (P < .001). The most commonly reported sunitinib-related grade 3 adverse events included hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%).
CONCLUSION
Sunitinib demonstrates longer overall survival compared with IFN-alpha plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC. The overall survival highlights an improved prognosis in patients with RCC in the era of targeted therapy.
目的
一项随机III期试验表明，在转移性肾细胞癌（RCC）的一线治疗中，舒尼替尼在无进展生存期（主要终点）方面优于干扰素α（IFN-α）。报告了最终生存分析和更新结果。
患者与方法
750例初治的转移性透明细胞RCC患者被随机分配至接受舒尼替尼治疗组，50mg口服，每日1次，按4周用药、2周停药的方案给药；或接受IFN-α治疗组，9MU皮下注射，每周3次。通过双侧对数秩检验和Wilcoxon检验比较总生存期。采用更新的随访评估无进展生存期、缓解率和安全性终点。
结果
根据未分层对数秩检验的初步分析，舒尼替尼组的中位总生存期长于IFN-α组（分别为26.4个月和21.8个月；风险比[HR]=0.821；95%CI，0.673至1.001；P=0.051）（未分层Wilcoxon检验P=0.013）。通过分层对数秩检验，HR为0.818（95%CI，0.669至0.999；P=0.049）。在IFN-α组中，33%的患者在试验停药后接受了舒尼替尼治疗，32%的患者接受了其他血管内皮生长因子信号抑制剂治疗。舒尼替尼组的中位无进展生存期为11个月，而IFN-α组为5个月（P<0.001）。舒尼替尼的客观缓解率为47%，而IFN-α为12%（P<0.001）。最常报告的与舒尼替尼相关的3级不良事件包括高血压（12%）、疲劳（11%）、腹泻（9%）和手足综合征（9%）。
结论
在转移性RCC患者的一线治疗中，舒尼替尼与IFN-α相比，总生存期更长，缓解率和无进展生存期有所改善。总生存期突出了靶向治疗时代RCC患者预后的改善。
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