Phase III Trial of Bevacizumab Plus Interferon Alfa-2a in Patients With Metastatic Renal Cell Carcinoma (AVOREN): Final Analysis of Overall Survival -- Escudier et al. 28 (13): 2144 -- Journal of Clinical Oncology

Originally published as JCO Early Release 10.1200/JCO.2009.26.7849 on April 5 2010
Journal of Clinical Oncology, Vol 28, No 13 (May 1), 2010: pp. 2144-2150
© 2010 American Society of Clinical Oncology.
This Article

Phase III Trial of Bevacizumab Plus Interferon Alfa-2a in Patients With Metastatic Renal Cell Carcinoma (AVOREN): Final Analysis of Overall Survival

Bernard Escudier, Joaquim Bellmunt, Sylvie Négrier, Emilio Bajetta, Bohuslav Melichar, Sergio Bracarda, Alain Ravaud, Sophie Golding, Sangeeta Jethwa, Vesna Sneller
From the Institut Gustave Roussy, Villejuif; Centre Léon Bérard, Lyon; Hôpital Saint André, Centre Hospitalier Universitaire de Bordeaux, France; Hospital del Mar, Barcelona, Spain; Ospedaliera Instituto, Milano; Ospedale San Donato, Arezzo, Italy; Charles University Medical School Teaching Hospital, Hradec Králové and Palack University Medical School and Teaching Hospital, Olomouc, Czech Republic; and F. Hoffmann-La Roche, Basel, Switzerland.

Corresponding author: Bernard Escudier, MD, Unité Immunothérapie, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France; e-mail: escudier@igr.fr.

Purpose A phase III trial of bevacizumab combined with interferon alfa-2a (IFN) showed significant improvements in progression-free survival (PFS) in metastatic renal cell carcinoma (mRCC). Here, we report overall survival (OS) data.

Patients and Methods Six hundred forty-nine patients with previously untreated mRCC were randomly assigned to receive bevacizumab (10 mg/kg every 2 weeks) plus IFN (9 MIU subcutaneously three times a week; n = 327) or IFN plus placebo (n = 322) in a multicenter, randomized, double-blind, phase III trial. The primary end point was OS. Final analysis of the secondary end point (PFS) was reported earlier.

Results Median OS was 23.3 months with bevacizumab plus IFN and 21.3 months with IFN plus placebo (unstratified hazard ratio [HR] = 0.91; 95% CI, 0.76 to 1.10; P = .3360; stratified HR = 0.86; 95% CI, 0.72 to 1.04; P = .1291). Patients (> 55%) in both arms received at least one postprotocol antineoplastic therapy, possibly confounding the OS analysis. Patients receiving postprotocol therapy including a tyrosine kinase inhibitor had longer median OS (bevacizumab plus IFN arm: 38.6 months; IFN plus placebo arm: 33.6 months; HR = 0.80; 95% CI, 0.56 to 1.13). Tolerability was similar to that reported previously.

Conclusion Bevacizumab plus IFN is active as first-line treatment in patients with mRCC. Most patients with mRCC receive multiple lines of therapy, so considering the overall sequence of therapy when selecting first-line therapy may optimize patient benefit.

See accompanying article on page 2137

Written on behalf of the AVOREN investigators.

Supported by F. Hoffmann-La Roche, Basel, Switzerland.

Presented in part at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29 to June 2, 2009, Orlando, FL.

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

Clinical trial information can be found for the following: BO17705E.




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Phase III Trial of Bevacizumab Plus Interferon Alfa-2a in Patients With Metastatic Renal Cell Carcinoma (AVOREN): Final Analysis of Overall Survival -- Escudier et al. 28 (13): 2144 -- Journal of Clinical Oncology