4513 Background: Tivozanib (T) is a potent, selective inhibitor of all three VEGF receptors with a long half-life of 4.5–5.1 days. Superior progression-free survival (PFS) and overall response rate (ORR) with T versus sorafenib (S) were demonstrated in a Phase III trial (TIVO-1) in patients (pts) with metastatic renal cell carcinoma (mRCC) (in ITT population, PFS: 11.9 vs 9.1 months HR=0.797, 95% CI 0.639–0.993; P=0.042; ORR: 33% vs 23%, P=0.014). Hypertension was more common with T, while lower rates of certain off-target AEs and fewer dose adjustments relative to S were reported (J Clin Oncol 2012;30[suppl]:Abstract 4501). Here we present efficacy and safety analyses for the pre-specified subset of pts who received no prior systemic therapy for mRCC. Methods: In the ITT population (N=517), pts were treatment-naïve or had received no more than 1 prior systemic therapy for metastatic disease; pts receiving prior VEGF- or mTOR-targeted therapy were excluded. Pts were randomized 1:1 to T 1.5 mg/d (once daily, 3 weeks on, 1 week off) or S 400 mg/d (twice daily, continuously). Of these, 181 pts (70%) in each treatment arm had not received prior systemic therapy for mRCC. Results: In pts who received no prior systemic therapy for mRCC, demographics were well balanced between the 2 arms. Median PFS was 12.7 for T vs 9.1 months for S (HR=0.756, 95% CI 0.580–0.985, P=0.037). ORR was 34% for T vs 24% for S (P=0.038). The most common adverse event (AE; All grades/Grade ≥3) for T was hypertension (T: 40%/25% vs S: 35%/18%), suggesting “on-target” biological activity and was manageable medically, while the most common AE for S was hand-foot syndrome (T: 11%/2% vs S: 52%/16%). Other common AEs were diarrhea (T: 22%/2% vs S: 32%/7%), fatigue (T: 19%/6% vs S: 15%/3%), and weight decrease (T: 18%/1% vs S: 17%/2%). Dose reduction (T: 12% vs S: 42%) and interruption (T: 18% vs S: 35%) rates were lower in the T arm and similar to the ITT population. Conclusions: T demonstrated significant improvement in PFS and ORR compared with S in pts who had received no prior systemic therapy for metastatic RCC. T was generally well tolerated, with low rates of treatment-related reduction/interruption in this pre-specified subgroup of pts. Clinical trial information: NCT01030783.
Next Steps: Sequencing Therapies in Metastatic Kidney Cancer in the Contemporary Era