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

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.