905P - CORE-URO-01 study: comparison of safety and efficacy of pazopanib in first-line metastatic renal cell carcinoma (mRCC) with or without renal failure

Abstract

Background: Pazopanib has been approved for first-line treatment of patients (pts) with mRCC based on the prospective randomized trial that enrolled only pts with adequate renal function. There are no data on the efficacy and toxicity of pazopanib in pts with renal insufficiency (RI). The aim of this study is to investigate the effect of kidney function on treatment outcomes in pts treated with pazopanib for mRCC. Methods: We retrospectively analyzed the data of the mRCC pts treated with pazopanib with respect to renal function in fourteen Italian institutions from January 2010 to June 2016. Baseline glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula at the time of therapy initiation. Pts with MDRD<60 mL/min/1.73 m2 (group A) were compared with pts with MDRD≥60 mL/min/1.73 m2 (group B) in terms of response rates, progression free survival (PFS), overall survival (OS) and toxicities. Results: Two hundred and twenty-nine pts with mRCC were included in this study: 128 pts in group A and 101 pts in group B. 68% of pts were male, median age was 67 years (34-88) and median CrCl was 49,7 ml/min in group A. In group B, 64% of pts were male, median age was 64 years (38-85) and median CrCl was 74 ml/min. Pts with MDRD<60 were more likely to have had a previous nephrectomy (87% vs 79%). Median PFS was 14 months (95% confidence interval [CI] 9.4-18.5) and 17 months (95% CI 11.4-22.8), OS was 30.5 months (95% CI 8-53) and 41.4 months (95% CI 21-62) for MDRD<60 group and MDRD≥60 respectively, with no statistical difference (p = 0.6). The disease control rate was 84% in group A, and 73% in group B (p = 0.1). About toxicity profile, no difference between the 2 groups was reported in terms of incidence of grade 1-2 (73% in group A vs 74% in group B, p = 0.5) and grade 3-4 (24% vs 33% respectively, p = 0.2). Dose reductions are statistically more frequent in pts in group A (66% vs 36%, p = 0.04), despite the same percentage of pts in both groups started at dose of 800 mg/day. Conclusions: Although in this study it is necessary to reduce the dose of pazopanib more frequent in pts with RI, kidney function at therapy initiation does not adversely affect the efficacy and safety of pazopanib. Legal entity responsible for the study: Cristina Masini Funding: None Disclosure: All authors have declared no conflicts of interest.