Axitinib is a second generation oral VEGFR-1, 2, and 3 selective inhibitor that blocks VEGFR receptors at nanomolar drug concentration levels while achieving minimal inhibition of other target proteins and has a short half-life in humans. Axitinib is primarily used in the treatment of progressive renal cell carcinoma that has failed prior treatment with a tyrosine kinase inhibitor or cytokine. A phase III randomized trial (AXIS) compared the efficacy of axitinib with sorafenib for the treatment of patients who had failed cytokine or other targeted drug therapy. The trial included 723 patients randomized to axitinib with an overall median progression-free survival of 6.7 months in the axitinib group and 4.7 months in the sorafenib group (HR=0.67; 95% CI: 0.54 to 0.81), an improvement of 40.0%. The most significant difference in progression-free survival was seen in patients who were not effective with cytokine therapy. For patients who were not effective with sunitinib treatment (n=194 in the axitinib group and n=195 in the sorafenib group), progression-free survival was 4.8 months (95% CI, 4.5 to 6.4) in the axitinib group and 3.4 months (95% CI, 2.6 to 4.7) in the sorafenib group. the AXIS trial showed grade 3-4 toxic effects of axitinib, including diarrhea, hypertension and malaise. This study initially established axitinib as a second-line treatment for metastatic kidney cancer.