Background: An extension and open access study allowed follow up of patients (pts) from TIVO-1 (301), an open label, phase III multinational trial in which pts with metastatic renal cell carcinoma (mRCC) were randomized to either tivozanib or sorafenib (both VEGF TKIs). TIVO-1 met its primary endpoint of improved median progression free survival (PFS) over sorafenib, but overall survival (OS) was shorter (J Clin Oncol. 2013; 31:3791). Follow up analysis of all pts from that trial is presented. Methods: Pts were treated until documented progression or unacceptable tolerability on both treatments. These pts were followed for OS, investigator assessed PFS, and long term safety. The majority of pts who received first line tivozanib had no subsequent therapy; the majority of pts initially treated with sorafenib were crossed over to tivozanib per protocol. Results: Few second line therapy options were available to pts who discontinued initial tivozanib. Of the 259 tivozanib pts, 69.3% received no subsequent therapy, 11.7% VEGF therapy (not tivozanib), 9.7% mTOR inhibitor therapy, and 10.0% non-targeted therapy. All 257 pts discontinued initial sorafenib therapy and 168 (65.4%) went on to subsequent VEGF therapy (163 treated with tivozanib), 1.2% to mTOR, 2.0% to non targeted therapy, and 31.5% to no additional therapy. Follow up PFS and OS from initial randomization for the 260 pts originally receiving tivozanib was 14.6 and 29.0 mos, and for the 257 pts originally receiving sorafenib was 9.7 and 34.1 mos, respectively (PFS HR = 0.77, OS HR = 1.18). Long term safety assessment of pts who continued tivozanib indicated that incidence of the most common on target AEs (hypertension and dysphonia) decreased over time. For the 163 pts who crossed over from sorafenib to second line tivozanib, median PFS was 11 mos and median OS was 21.6 mos from the start of second line tivozanib. Conclusions: This long term analysis of PFS and OS underscores the positive impact of tivozanib treatment after sorafenib failure in mRCC. Lack of access to second line therapies in pts in the tivozanib arm due to geographical reasons most likely affected trial results. Clinical trial information: NCT01030783, NCT01076010, NCT01369433