Axitinib is a second-generation oral VEGFR-1, 2, and 3 selective inhibitor that blocks the VEGFR receptor at nanomolar drug concentration levels while achieving minimal inhibition of other target proteins and has a short half-life in humans. A phase III randomized trial (AXIS) compared the efficacy of axitinib with sorafenib for the treatment of patients who were not responding to cytokine or other targeted drug therapy. The trial enrolled 723 patients randomized to axitinib and improved their median progression-free survival from 5 months to 7 months, an improvement of 40.0 percent. The overall median progression-free survival was 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). 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 that axitinib had no less than grade 3 toxic effects, including 11.0 percent of patients with diarrhea, 16.0 percent with hypertension, and 11.0 percent with malaise. This study initially established axitinib as a second-line treatment for metastatic kidney cancer. However, a recently reported analysis of overall survival showed that overall survival was similar in the axitinib and sorafenib groups, 20.1 months for axitinib and 19.2 months for sorafenib, with no significant difference.