Activity of tivozanib in non-clear cell renal cell carcinoma (nccRCC): Subgroup analysis from a phase 2 randomized discontinuation trial.

4542 Background: Non-clear cell renal cell carcinoma (nccRCC) is a blanket term for a collection of heterogenous and biologically diverse RCC histologies including (but not limited to) papillary, chromophobe and unclassified subtypes. Tivozanib is a selective VEGFR tyrosine kinase inhibitor with demonstrated activity in RCC with clear cell component. Here we report efficacy of tivozanib in a histologically diverse nccRCC subset included in a phase 2 study. Methods: We conducted a subgroup analysis of patients with nccRCC enrolled in the study 201 (NCT00502307), a phase 2 randomized discontinuation trial of tivozanib in patients with RCC who had no prior VEGF targeted treatment. Clinical outcomes including overall response rate (ORR), disease control rate (DCR, defined by CR+PR+SD), and progression free survival (PFS) were examined. Safety outcomes for all patients are reported in the original publication (Nosov, JCO 2012). Results: Of the 272 patients enrolled, 46 (16.9%) patients had nccRCC. [11 (4%) papillary, 2 (0.7%) chromophobe, 2 (0.7%) collecting duct, and 31 (11.4%) unclassified/mixed]. Of the 46 nccRCC patients, the ORR was 17.4% by investigator (INV) review and 15.2% by independent radiology review (IRR). The DCR was 80.4% by INV and IRR. The median PFS was 6.7 months (204 days) (95%CI: 125-366 days) by IRR (Figure 1). Of note, 14 patients with SD after 16 weeks on tivozanib were randomized to 12 weeks of placebo and may have progressed during that timeframe before unblinding and resuming tivozanib. Safety was not analyzed by histology but there were no new safety signals and was consistent with tivozanib labelling in the ITT population. Conclusions: Tivozanib demonstrated activity and a favorable safety profile in patients with nccRCC. This data adds to the body of evidence supporting VEGFR TKI use in advanced RCC including in non-clear cell histologies. Clinical trial information: NCT00502307. [Table: see text]