The impact of kidney function on the efficacy and safety of pazopanib in metastatic renal cell carcinoma (mRCC) patients: CORE-URO-01 study.

Abstract

e16063 Background: Pazopanibhas been approved for treatment of patients (pts) with mRCC based on the prospective randomized trial that enrolled only pts with adequate renal parameters. There are no data on the toxicity profile and efficacy of pazopanib in pts with renal insufficiency (RI).The aim of this study is to investigate the effect of renal 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 eleven 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 1) were compared with pts with MDRD ≥60 mL/min/1.73 m2(group 2) in terms of response rates, progression free survival (PFS), overall survival (OS) and side effects. Results: One hundred and twenty-ninepts with mRCC were included in this study: 70 pts in group 1 and 59 pts in group 2. 67% of pts were male, median age was 66 years (34-83) and median CrCl was 49 ml/min (6.3-59.5) in group 1. In group 2, 64% of pts were male, median age was 65 years (38-80), and median CrCl was 64 ml/min (58.1-137.1) Pts with MDRD < 60 were more likely to have had a previous nephrectomy (84.3% vs 79.7%). No difference between the 2 groups was observed in terms of outcomes: PFS was 9.6 months (0.6–56.9) and 9.0 months (0.4–60.1), OS was 16.1 months (1.3–56.9) and 17.0 months (1.2–60.1), for MDRD < 60 group and MDRD ≥60 respectively. The disease control rate was 85.8% in group 1, and 72.9% in group 2. About grade 1-2 toxicity, no difference between the 2 groups was reported (67.1% vs 67.8%) while a higher incidence of grade 3-4 toxicity was evident in the group 1 (25.7% vs 18.6%). Conclusions: RI was commonly observed in pts with mRCC. Renal function at therapy initiation does not adversely affect the efficacy and safety of pazopanib. More frequent monitoring of side-effects in patients with RI is recommended.