Rini Brian I, Halabi Susan, Rosenberg Jonathan E, Stadler Walter M, Vaena Daniel A, Ou San-San, Archer Laura, Atkins James N, Picus Joel, Czaykowski Piotr, Dutcher Janice, Small Eric J
Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA.
J Clin Oncol. 2008 Nov 20;26(33):5422-8. doi: 10.1200/JCO.2008.16.9847. Epub 2008 Oct 20.
Bevacizumab is an antibody that binds to vascular endothelial growth factor (VEGF) and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN) is a historic standard first-line treatment for RCC. A prospective, randomized phase III trial of bevacizumab plus IFN versus IFN monotherapy was conducted.
Patients with previously untreated, metastatic clear-cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN (9 million U subcutaneously three times weekly) or the same dose and schedule of IFN 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 (ORR), and safety.
Between October 2003 and July 2005, 732 patients were enrolled. The prespecified stopping rule for OS has not yet been reached. The median PFS was 8.5 months in patients receiving bevacizumab plus IFN (95% CI, 7.5 to 9.7 months) versus 5.2 months (95% CI, 3.1 to 5.6 months) in patients receiving IFN monotherapy (log-rank P < .0001). The adjusted hazard ratio was 0.71 (95% CI, 0.61 to 0.83; P < .0001). Bevacizumab plus IFN had a higher ORR as compared with IFN (25.5% [95% CI, 20.9% to 30.6%] v 13.1% [95% CI, 9.5% to 17.3%]; P < .0001). Overall toxicity was greater for bevacizumab plus IFN, including significantly more grade 3 hypertension (9% v 0%), anorexia (17% v 8%), fatigue (35% v 28%), and proteinuria (13% v 0%).
Bevacizumab plus IFN produces a superior PFS and ORR in untreated patients with metastatic RCC as compared with IFN monotherapy. Toxicity is greater in the combination therapy arm.
贝伐单抗是一种可与血管内皮生长因子（VEGF）结合的抗体，对转移性肾细胞癌（RCC）具有活性。干扰素α（IFN）是RCC的一种传统标准一线治疗方法。开展了一项贝伐单抗联合IFN对比IFN单药治疗的前瞻性、随机III期试验。
在一项多中心III期试验中，将既往未接受治疗的转移性透明细胞RCC患者随机分配，分别接受贝伐单抗（每2周静脉注射10mg/kg）联合IFN（皮下注射900万单位，每周3次）或相同剂量和疗程的IFN单药治疗。主要终点为总生存期（OS）。次要终点为无进展生存期（PFS）、客观缓解率（ORR）和安全性。
2003年10月至2005年7月期间，共纳入732例患者。OS的预先设定的停止规则尚未达到。接受贝伐单抗联合IFN治疗的患者中位PFS为8.5个月（95%CI，7.5至9.7个月），而接受IFN单药治疗的患者为5.2个月（95%CI，3.1至5.6个月）（对数秩检验P<.0001）。校正风险比为0.71（95%CI，0.61至0.83；P<.0001）。与IFN相比，贝伐单抗联合IFN的ORR更高（25.5%[95%CI，20.9%至30.6%]对13.1%[95%CI，9.5%至17.3%]；P<.0001）。贝伐单抗联合IFN的总体毒性更大，包括3级高血压（9%对0%）、厌食（17%对8%）、疲劳（35%对28%）和蛋白尿（13%对0%）显著更多。
与IFN单药治疗相比，贝伐单抗联合IFN在未治疗的转移性RCC患者中产生了更好的PFS和ORR。联合治疗组的毒性更大。
