Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206

Abstract

Purpose: 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 and methods: 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.

Results: 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%).

Conclusion: 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.

Fig A1.

Kaplan-Meier progression-free survival probability curves by the two treatment arms according to the number of adverse risk features. (A) Kaplan-Meier progression-free survival in patients with zero adverse risk features receiving bevacizumab plus interferon alfa (IFN) versus IFN monotherapy; (B) Kaplan-Meier progression-free survival in patients with one to two adverse risk features; (C) Kaplan-Meier progression-free survival in patients with three or more adverse risk features.

Fig 1.

CONSORT diagram. IFN, interferon alfa.

Fig 2.

Kaplan-Meier progression-free survival probability curves by the two treatment arms. Progression-free survival in patients receiving bevacizumab plus interferon alfa (IFN) was 8.5 months (95% CI, 7.5 to 9.7 months) compared with 5.2 months (95% CI, 3.1 to 5.6 months) in patients receiving IFN monotherapy (P < .0001).