Phase III Trial of Bevacizumab Plus Interferon Alfa Versus Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Final Results of CALGB 90206
Phase III Trial of Bevacizumab Plus Interferon Alfa Versus Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Final Results of CALGB 90206
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DOI：
10.1200/jco.2009.26.5561
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发表时间：
2010-05-01
影响因子：
45.3
通讯作者：
Small, Eric J.
中科院分区：
文献类型：
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作者：
Rini, Brian I.;Halabi, Susan;Small, Eric J.
目的贝伐珠单抗是一种结合血管内皮生长因子的抗体，对转移性肾细胞癌 (RCC) 具有活性。干扰素α（IFN-α）是肾细胞癌历史上的标准初始治疗方法。进行了一项贝伐珠单抗加 IFN-α 与 IFN-α 单药治疗的前瞻性、随机、III 期试验。 患者和方法 在一项多中心 III 期试验中，先前未经治疗的转移性透明细胞 RCC 患者被随机分配接受贝伐珠单抗（每 2 周静脉注射 10 mg/kg）加 IFN-α（每周 3 次皮下注射 900 万单位）或接受相同剂量和方案的 IFN-α 单药治疗。主要终点是总生存期（OS）。次要终点是无进展生存期 (PFS)、客观缓解率和安全性。结果 732 名患者入组。贝伐单抗联合 IFN-α 的中位 OS 时间为 18.3 个月（95% CI，16.5 至 22.5 个月），IFN-α 单药治疗的中位 OS 时间为 17.4 个月（95% CI，14.4 至 20.0 个月）（未分层对数秩 P = 0.097）。调整分层因素后，贝伐单抗加 IFN-α 的风险比为 0.86（95% CI，0.73 至 1.01；分层对数秩 P = 0.069）。贝伐单抗加 IFN-α 治疗后 3 至 4 级高血压 (HTN)、厌食、疲劳和蛋白尿的发生率显着增加。与未患 HTN 的患者相比，接受贝伐珠单抗加 IFN-α 治疗后出现 HTN 的患者的 PFS 和 OS 显着改善。结论 OS 倾向于贝伐珠单抗加 IFN-α 组，但不符合预先定义的显着性标准。 HTN 可能是贝伐珠单抗加 IFN-α 治疗结果的生物标志物。
PurposeBevacizumab is an antibody that binds vascular endothelial growth factor and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN-alpha) is the historic standard initial treatment for RCC. A prospective, randomized, phase III trial of bevacizumab plus IFN-alpha versus IFN-alpha monotherapy was conducted.Patients and MethodsPatients with previously untreated, metastatic clear cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN-alpha (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN-alpha monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate, and safety.ResultsSeven hundred thirty-two patients were enrolled. The median OS time was 18.3 months (95% CI, 16.5 to 22.5 months) for bevacizumab plus IFN-alpha and 17.4 months (95% CI, 14.4 to 20.0 months) for IFN-alpha monotherapy (unstratified log-rank P = .097). Adjusting on stratification factors, the hazard ratio was 0.86 (95% CI, 0.73 to 1.01; stratified log-rank P = .069) favoring bevacizumab plus IFN-alpha. There was significantly more grade 3 to 4 hypertension (HTN), anorexia, fatigue, and proteinuria for bevacizumab plus IFN-alpha. Patients who developed HTN on bevacizumab plus IFN-alpha had a significantly improved PFS and OS versus patients without HTN.ConclusionOS favored the bevacizumab plus IFN-alpha arm but did not meet the predefined criteria for significance. HTN may be a biomarker of outcome with bevacizumab plus IFN-alpha.