An open-label extension study to evaluate safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC)

Abstract

5110 Background: The efficacy and safety of pazopanib (paz), a multikinase angiogenesis inhibitor, was evaluated in a randomized, double-blind placebo-controlled phase III study (VEG105192), in treatment-naïve and cytokine-pretreated patients (pts) with advanced RCC. Pts with progressive disease (PD) on placebo had the option to receive paz 800 mg QD via an extension study (VEG107769). Methods: Pts with ECOG PS ≤ 2, adequate organ function and no other systemic anticancer treatment since PD on VEG105192 were eligible. The primary endpoint was safety. Secondary endpoints included response rate (RR) per RECIST and progression-free survival (PFS). RR was described along with 95% confidence intervals (CIs). PFS was summarized descriptively using Kaplan-Meier estimates for the median, quartiles and PFS rates at 6, 12, and 18 mo along with approximate 95% CIs. Results: 70 placebo pts were enrolled (+ 1 paz pt as an exemption due to symptom improvement). 34 pts (48%) were treatment-naïve and 37 (52%) were cytokine pretreated (at baseline in VEG105192). Median age was 59 y (25–80); baseline ECOG PS 0 (32%), 1 (52%), and 2 (14%). Median time from randomization to placebo in VEG105192 to start of paz treatment on VEG107769 was 6.4 mo (1–18 mo). At VEG107769 clinical cut-off (May 08), 21 (30%) pts had died, 40 (56%) pts had discontinued paz, and 31 (44%) pts were still on paz. Median exposure to paz was 5.7 mo. Most pts died or discontinued paz due to PD. The majority of adverse events (AEs) were Gr 1/2. Gr 3/4 AEs were experienced by 21%/7% of pts. The most common AEs were hypertension (46%; 4% Gr 3/4), hair color changes (39%; 0% Gr 3/4), diarrhea (38%; 1% Gr 3/4), anorexia (24%; 1% Gr 3/4), and nausea (24%; 0% Gr 3/4). Two pts had fatal AEs: sudden death and gastrointestinal hemorrhage. The most common Gr 3 chemistry laboratory abnormalities were hyponatremia (7%) and elevated ALT (7%) and AST (6%); no Gr 4. RR was 32.4% (95% CI: 21.5, 43.3); median PFS was 8.3 mo (95% CI: 6.1, 11.4 mo). Conclusions: Patients with advanced RCC who developed PD on placebo in a phase III study subsequently achieved clinical benefit from paz treatment in this extension study. These findings support the continued evaluation of paz in advanced RCC. [Table: see text]