Patient preference between pazopanib (Paz) and sunitinib (Sun): Results of a randomized double-blind, placebo-controlled, cross-over study in patients with metastatic renal cell carcinoma (mRCC)—PISCES study, NCT 01064310.

Abstract

CRA4502 Background: Increasingly pt reported outcomes are being added to traditional efficacy outcomes to understand the clinical relevance of toxicity differences between therapies. This study investigated if tolerability differences were significant enough to lead a patient to prefer continuing their treatment with Paz or Sun. Methods: Pts with mRCC were randomized 1:1 to receive as first line treatment blinded 800mg Paz for 10 weeks followed by a 2-week washout and then 50mg Sun for 10 weeks (4/2 weeks schedule) or vice versa. Pts were stratified based on ECOG performance status (0 vs 1) and number of metastatic sites (0/1 vs 2+). The primary endpoint, patient preference assessed at 22 weeks, was compared using Prescott’s test (α=0.10). At least 102 of 160 planned pts were required to complete the preference questionnaire to provide 80% power to detect a preference for one drug over another of 50% vs 30% with 20% expressing no preference. Other endpoints included physician preference, safety, QoL, pharmacokinetics and biomarkers. Results: Of 168 randomized pts, 126 completed the preference questionnaire. In the protocol-driven primary analysis (n=114), Paz was preferred by 70% of pts, Sun by 22% and 8% had no preference. After adjusting for a modest sequence effect, the difference in preference was 49% [90% CI 37.0 – 61.5% p <0.001] in favor of Paz. All pre-planned sensitivity analyses conducted were statistically significant in favor of Paz, including one which imputed Sun for all unavailable pt preference data. The most common reasons for Paz preference were better QoL and less fatigue. 60% of physicians preferred Paz vs 21% for Sun vs 19% no preference. Adverse events (AE) were in line with known profiles for both drugs. Pts on Paz had fewer dose reductions (13% vs 20%) and interruptions (6% vs 12%) vs Sun, mostly due to AE. There was less fatigue on Paz as assessed by FACIT-Fatigue; treatment difference of 2.49, p=0.002. Investigator assessed response (RECIST 1.1) was 22% with Paz vs 24% with Sun, p=0.87. Conclusions: This innovative trial design clearly demonstrates the better tolerability of Paz compared to Sun.