Division of Drug Oncology Products, Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993-0002, USA.
Oncologist. 2010;15(4):428-35. doi: 10.1634/theoncologist.2009-0178. Epub 2010 Mar 23.
This report summarizes the U.S. Food and Drug Administration (FDA)'s approval of temsirolimus (Torisel), on May 30, 2007, for the treatment of advanced renal cell carcinoma (RCC). Information provided includes regulatory history, study design, study results, and literature review. A multicenter, three-arm, randomized, open-label study was conducted in previously untreated patients with poor-prognosis, advanced RCC. The study objectives were to compare overall survival (OS), progression-free survival (PFS), objective response rate, and safety in patients receiving interferon (IFN)-alpha versus those receiving temsirolimus alone or in combination with IFN-alpha. In the second planned interim analysis of the intent-to-treat population (n = 626), there was a statistically significant longer OS time in the temsirolimus (25 mg) arm than in the IFN-alpha arm (median, 10.9 months versus 7.3 months; hazard ratio [HR], 0.73; p = .0078). The combination of temsirolimus (15 mg) and IFN-alpha did not lead to a significant difference in OS compared with IFN-alpha alone. There was also a statistically significant longer PFS time for the temsirolimus (25 mg) arm than for the IFN-alpha arm (median, 5.5 months versus 3.1 months; HR, 0.66, p = .0001). Common adverse reactions reported in patients receiving temsirolimus were rash, asthenia, and mucositis. Common laboratory abnormalities were anemia, hyperglycemia, hyperlipidemia, and hypertriglyceridemia. Serious but rare cases of interstitial lung disease, bowel perforation, and acute renal failure were observed. Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-alpha and provides an additional treatment option for patients with advanced RCC.
本报告总结了美国食品药品监督管理局（FDA）于 2007 年 5 月 30 日批准替西罗莫司（Torisel）用于治疗晚期肾细胞癌（RCC）。提供的信息包括监管历史、研究设计、研究结果和文献综述。一项多中心、三臂、随机、开放性研究在未经治疗的预后不良的晚期 RCC 患者中进行。该研究的目的是比较接受干扰素（IFN）-α治疗的患者与单独接受替西罗莫司或与 IFN-α联合治疗的患者的总生存期（OS）、无进展生存期（PFS）、客观缓解率和安全性。在意向治疗人群（n = 626）的第二次计划中期分析中，替西罗莫司（25mg）组的 OS 时间明显长于 IFN-α组（中位数，10.9 个月对 7.3 个月；风险比[HR]，0.73；p =.0078）。替西罗莫司（15mg）与 IFN-α联合使用与单独使用 IFN-α相比，OS 无显著差异。替西罗莫司（25mg）组的 PFS 时间也明显长于 IFN-α组（中位数，5.5 个月对 3.1 个月；HR，0.66，p =.0001）。接受替西罗莫司治疗的患者报告的常见不良反应有皮疹、乏力和黏膜炎。常见的实验室异常包括贫血、高血糖、高脂血症和高甘油三酯血症。观察到严重但罕见的间质性肺病、肠穿孔和急性肾衰竭病例。替西罗莫司在 OS 和 PFS 方面优于 IFN-α，为晚期 RCC 患者提供了另一种治疗选择。
