Activity of tivozanib (AV-951) in patients with renal cell carcinoma (RCC): Subgroup analysis from a phase II randomized discontinuation trial (RDT).

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4599 Background: Tivozanib, a potent and selective inhibitor of VEGFR-1, 2, and 3 kinases, was tested in a phase II RDT that included patients (pts) with all histologies of RCC, as well as pts who had not undergone nephrectomy or had received prior therapy with cytokines or chemotherapy. The median PFS in all pts was 11.8 months [ASCO 2009; abstract #5032] Methods: A retrospective subgroup analysis was conducted in pts with RCC with clear cell component (CC), pts who had undergone nephrectomy (N), or both (CC+N). Subgroup analysis was also conducted to explore the effect of prior therapy. ORR and PFS were analyzed in pts who attained 25% regression during the first 16 wks, as well as pts who were randomized to placebo and subsequently crossed over to tivozanib after PD on placebo. Results: 272 pts were enrolled between Oct 2007 and July 2008: 83% had RCC with clear cell component, 73% had undergone nephrectomy, and 46% had received prior therapy. Based on a data cutoff of 31 Jan 2009, the ORR by independent radiology review (IRR) was 25.4% in all pts, 27.0% in CC, 28.1% in N, and 29.6% in CC+N. Median PFS was 11.8 mo in all pts, 12 mo in CC, 12 mo in N, and not reached in CC+N. Median PFS was similar in pts who had received prior therapy and those who were treatment naïve. The safety profile of tivozanib was similar to that reported previously, with hypertension (54.4%) and dysphonia (21%) as the most frequent treatment related adverse events (AEs) of any grade. There was a low incidence of fatigue (9.9%), diarrhea (10.7%), stomatitis (3.7%) and hand- foot syndrome (3.3%). With a median duration of treatment of 7.6 mo (range 0.02-15.4 mo), 8.5% pts required dose reduction and 2.9% required treatment interruption due to AEs. Conclusions: Pts with RCC with a clear cell component who have undergone nephrectomy appear to experience the greatest benefit from tivozanib with a median PFS that was not reached at the time of this analysis (based on IRR). Updated ORR and PFS results will be presented. The AE profile of tivozanib was consistent with that of a selective VEGFR inhibitor with minimal off-target toxicities. Tivozanib is currently being tested in a phase III trial in RCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AVEO AVEO

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