Background: In the AVOREN trial, BEV (Avastin) + IFN significantly improved PFS and ORR compared with placebo + IFN in pts with mRCC [Escudier, Lancet. 2007]. The study was unblinded after interim analysis due to significant superiority of BEV + IFN and the DSMB recommended crossover of pts from placebo to BEV (n = 13). We report here the results of the final analysis. Methods: Eligible pts had predominantly clear-cell mRCC, prior nephrectomy, no prior systemic therapy for metastatic disease, KPS [=]70%, no CNS metastases and adequate organ function. Pts were randomised to IFN (9MIU tiw) + BEV (10 mg/kg q2w) or placebo until disease progression. Primary endpoint was OS, with pre-planned stratified and unstratified analyses according to regional regulatory requirements. Results: 649 pts were randomised to BEV + IFN (n = 327) or placebo + IFN (n = 322). An independent radiological review confirmed previous investigator assessments, showing PFS of 10.4 vs 5.5 months (HR 0.57) and a response rate of 31% vs 12% in the two arms, verifying the robustness of the investigator analysis. At the time of final OS analysis (444 events), median follow-up was 22.9 months in the BEV arm and 20.6 months in the placebo arm. Final median OS stratified for region and Motzer score was 23.3 months in the BEV + IFN arm and 21.3 months in the IFN + placebo arm (HR 0.86 [95% CI: 0.72-1.04], p = 0.1291). No new or unexpected AEs were observed. More pts in the IFN + placebo arm than the BEV + IFN arm received post-protocol therapy, including TKIs, mTOR inhibitors, cytokines and chemotherapy: 180 (55%) in the BEV + IFN arm and 202 (63%) in the IFN + placebo arm. Exploratory analysis showed that median OS in pts receiving second-line TKI therapy (BEV + IFN, n = 96; IFN + placebo, n = 81) was 38.6 months vs 33.2 months (HR = 0.77 [95% CI: 0.51-1.15], p = 0.1948). Further subgroup analyses will be presented. Conclusions: BEV + IFN is a first-line standard of care for pts with mRCC, improving PFS and ORR, with a trend toward improved OS, compared with IFN. The observed OS results may have been influenced by subsequent anti-neoplastic therapy, which was not prespecified in the protocol and represents an uncontrolled element of the OS analysis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration F. Hoffmann-La Roche Ltd Antigenics, Bayer, F. Hoffmann-La Roche Ltd, GlaxoSmithKline, Inate Pharma, Novartis, Pfizer, Schering-Plough, Wyeth Antigenics, Bayer, F. Hoffmann-La Roche Ltd, Novartis, Pfizer, sanofi-aventis, Wyeth F. Hoffmann-La Roche Ltd, GlaxoSmithKline, Novartis, Wyeth Bayer, F. Hoffmann-La Roche Ltd, Novartis, Pfizer