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Clinical Trial
. 2010 May 1;28(13):2137-43.
doi: 10.1200/JCO.2009.26.5561. Epub 2010 Apr 5.

Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206

Brian I Rini  1 , Susan Halabi, Jonathan E Rosenberg, Walter M Stadler, Daniel A Vaena, Laura Archer, James N Atkins, Joel Picus, Piotr Czaykowski, Janice Dutcher, Eric J Small
Affiliations
Clinical Trial

Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206

Brian I Rini et al. J Clin Oncol. .

Abstract

Purpose: Bevacizumab 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 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-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.

Results: Seven 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.

Conclusion: OS 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.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram. IFN, interferon.
Fig 2.
Fig 2.
Overall survival (OS) according to treatment arm. IFN, interferon; BEV, bevacizumab.
Fig 3.
Fig 3.
Forest plot of overall survival of selected subgroups. HR, hazard ratio; IFN, interferon; Beva, bevacizumab; MSKCC, Memorial Sloan-Kettering Cancer Center; Mets, metastases.
Fig 4.
Fig 4.
Kaplan-Meier (A) overall survival and (B) progression-free survival according to development of grade ≥ 2 hypertension on bevacizumab plus interferon alfa.
See this image and copyright information in PMC

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