ABSTRACT Purpose In the phase III AXIS trial, axitinib prolonged progression-free survival (PFS) compared with sorafenib as 2nd-line therapy for metastatic renal cell carcinoma (mRCC) (Lancet 2011;378:1931). Mature overall survival (OS) data (as of Nov 1, 2011) are reported. Methods 723 patients (pts) with clear cell mRCC, progressive disease after 1 systemic therapy, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 were stratified by ECOG PS and prior therapy and randomised 1:1 to axitinib 5 mg twice daily (BID) or sorafenib 400 mg BID. OS was analysed as a secondary endpoint based on 425 events and compared using a 1-sided log-rank test stratified by ECOG PS and prior therapy. Pretreatment prognostic factors were studied by multivariate analyses. Pts were grouped by diastolic blood pressure (dBP) on therapy (≥1 dBP measurement ≥90 vs dBP Results Median OS (mOS) was 20.1 mo (95% confidence interval [CI]16.7, 23.4) in the axitinib arm and 19.2 mo (95% CI 17.5, 22.3) in the sorafenib arm; hazard ratio (HR) 0.969 (95% CI 0.800, 1.174); P = 0.3744. In prior therapy subsets, mOS with axitinib vs sorafenib was: prior cytokine, 29.4 vs 27.8 mo (HR 0.813; 95% CI 0.555, 1.191); prior sunitinib, 15.2 vs 16.5 mo (HR 0.997; 95% CI 0.782, 1.270); prior bevacizumab plus interferon-α, 14.7 vs 19.8 mo (HR 1.825; 95% CI 0.942, 3.535); and prior temsirolimus, 14.0 vs 8.5 mo (HR 0.459; 95% CI 0.165, 1.278). Prognostic factors for longer OS with 2nd-line therapy (P Conclusions Axitinib resulted in prolonged PFS and similar OS compared with sorafenib for 2nd-line mRCC. OS results and prognostic factors may be used in clinical trial design for novel agents in 2nd-line therapy. Disclosure R.J. Motzer: Pfizer Consultant. Research Funding from Pfizer. B. Escudier: Advisory role for Novartis, Bayer, Pfizer, Aveo, GSK. S. Negrier: Ad Board : Pfizer Honoraria: Novartis Research grants: GSK, Roche. M.E. Gore: Speaker bureau and advisory boards: Roche, GSK, Novartis, Bayer, Pfizer, Schering Plough, Bristol Myers Squibb, Aveo, AstraZeneca, Astellas. J. Tarazi: Employee of and own stock in Pfizer. S. Hariharan: Employee of and own stock in Pfizer. B. Rosbrook: Employee of and own stock in Pfizer. S. Kim: Employee of and own stock in Pfizer. B.I. Rini: Consulting and research funding from Pfizer. All other authors have declared no conflicts of interest.