Background: Axitinib is a potent, selective inhibitor of VEGF receptors. In a randomized, double-blind, phase II study in patients with metastatic renal cell carcinoma, median overall survival (OS) was 42.7 months who underwent axitinib titration versus (vs.) 30.4 months in placebo titration (hazard ratio [HR]: 0.785; 95% confidence interval: 0.485, 1.272). OS Kaplan-Meier curves for two arms appeared to cross over at approximately 24 months and thus we investigated baseline characteristics associated with OS benefit from axitinib titration. Methods: Patients received axitinib 5 mg twice daily (BID) for 28 days. Patients who met the dose titration criteria were randomized 1:1 to axitinib titration or placebo titration. Patients who did not meet the dose titration criteria continued axitinib 5 mg BID. Baseline characteristics were compared between patients with OS ≥ 24 and < 24 months who were randomized to axitinib titration and subsequently, multivariate analysis for baseline characteristics was conducted to investigate effect of interaction with axitinib titration. Results: Fifty-six patients underwent axitinib titration with 53 evaluable for this analysis. Thirty-three patients had an OS ≥ 24 months and had significantly fewer metastatic sites (≤2, ≥3: 52/48% vs. 10/90%), compared to the 20 patients with OS < 24 months. In addition, a lower percentage of patients with OS ≥ 24 months had lymph node metastasis (45 vs. 75%), liver metastasis (15 vs. 45%), duration from diagnosis to treatment <1 year (36 vs. 85%), and baseline hemoglobin (Hb) < LLN (lower limit of normal) (33 vs. 75%), compared to the patients with OS < 24 months. In multivariate analysis in total of 112 patients who were randomized to axitinib or placebo titration, duration from diagnosis and baseline Hb were significantly associated with favorable OS with axitinib titration (p<0.1). Conclusions: Duration from diagnosis and baseline Hb are associated with favorable OS with axitinib titration. Clinical trial information: NCT00835978