随机 III 期试验：替西罗莫司联合贝伐珠单抗与干扰素 α 联合贝伐珠单抗治疗转移性肾细胞癌：INTORACT 试验。
Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa and bevacizumab in metastatic renal cell carcinoma: INTORACT trial.
机构信息
Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Joaquim Bellmunt, University Hospital del Mar-IMIM, Barcelona, Spain; Jill Clancy, Kongming Wang, Andreas G. Niethammer, Subramanian Hariharan, Pfizer, New York, NY; and Bernard Escudier, Institut Gustave Roussy, Villejuif, France.
出版信息
J Clin Oncol. 2014 Mar 10;32(8):752-9. doi: 10.1200/JCO.2013.50.5305. Epub 2013 Dec 2.
PURPOSE
To prospectively determine the efficacy of combination therapy with temsirolimus plus bevacizumab versus interferon alfa (IFN) plus bevacizumab in metastatic renal cell carcinoma (mRCC).
PATIENTS AND METHODS
In a randomized, open-label, multicenter, phase III study, patients with previously untreated predominantly clear-cell mRCC were randomly assigned, stratified by prior nephrectomy and Memorial Sloan-Kettering Cancer Center prognostic group, to receive the combination of either temsirolimus (25 mg intravenously, weekly) or IFN (9 MIU subcutaneously thrice weekly) with bevacizumab (10 mg/kg intravenously, every 2 weeks). The primary end point was independently assessed progression-free survival (PFS).
RESULTS
Median PFS in patients treated with temsirolimus/bevacizumab (n = 400) versus IFN/bevacizumab (n = 391) was 9.1 and 9.3 months, respectively (hazard ratio [HR], 1.1; 95% CI, 0.9 to 1.3; P = .8). There were no significant differences in overall survival (25.8 ν 25.5 months; HR, 1.0; P = .6) or objective response rate (27.0% ν 27.4%) with temsirolimus/bevacizumab versus IFN/bevacizumab, respectively. Patients receiving temsirolimus/bevacizumab reported significantly higher overall mean scores in the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) -15 and FKSI-Disease Related Symptoms subscale compared with IFN/bevacizumab (indicating improvement); however, no differences in global health outcome measures were observed. Treatment-emergent all-causality grade ≥ 3 adverse events more common (P < .001) with temsirolimus/bevacizumab were mucosal inflammation, stomatitis, hypophosphatemia, hyperglycemia, and hypercholesterolemia, whereas neutropenia was more common with IFN/bevacizumab. Incidence of pneumonitis with temsirolimus/bevacizumab was 4.8%, mostly grade 1 or 2.
CONCLUSION
Temsirolimus/bevacizumab combination therapy was not superior to IFN/bevacizumab for first-line treatment in clear-cell mRCC.
目的
前瞻性评估替西罗莫司联合贝伐单抗对比干扰素α（IFN）联合贝伐单抗治疗转移性肾细胞癌（mRCC）的疗效。
方法
在一项随机、开放标签、多中心、III 期研究中，按既往是否接受过肾切除术和 Memorial Sloan-Kettering 癌症中心预后分组进行分层，将未经治疗的主要为透明细胞 mRCC 患者随机分配接受替西罗莫司（静脉注射，每周 25mg）联合贝伐单抗（静脉注射，每 2 周 10mg/kg）或 IFN（皮下注射，每周 3 次，每次 9MIU）联合贝伐单抗治疗。主要终点是独立评估无进展生存期（PFS）。
结果
接受替西罗莫司/贝伐单抗（n = 400）和 IFN/贝伐单抗（n = 391）治疗的患者中位 PFS 分别为 9.1 和 9.3 个月（风险比[HR]，1.1；95%置信区间，0.9 至 1.3；P =.8）。替西罗莫司/贝伐单抗与 IFN/贝伐单抗相比，总生存（25.8 ν 25.5 个月；HR，1.0；P =.6）或客观缓解率（27.0% ν 27.4%）均无显著差异。与 IFN/贝伐单抗相比，接受替西罗莫司/贝伐单抗治疗的患者在癌症治疗功能评估-肾脏症状指数（FKSI）-15 和 FSKI-疾病相关症状子量表中的总平均评分显著更高（表明改善）；然而，在全球健康结局测量方面没有观察到差异。替西罗莫司/贝伐单抗治疗相关的所有病因≥3 级不良事件更常见（P <.001），包括黏膜炎症、口腔炎、低磷血症、高血糖和高胆固醇血症，而 IFN/贝伐单抗更常见中性粒细胞减少症。替西罗莫司/贝伐单抗治疗的肺炎发生率为 4.8%，主要为 1 级或 2 级。
结论
替西罗莫司/贝伐单抗联合治疗在透明细胞 mRCC 的一线治疗中并不优于 IFN/贝伐单抗。
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