Quality-adjusted time without symptoms or toxicity analysis of pazopanib versus sunitinib in patients with renal cell carcinoma.

Overview

abstract

BACKGROUND: In a phase 3, randomized, open-label trial (Pazopanib versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma, COMPARZ; NCT00720941), pazopanib was found to be noninferior to sunitinib in terms of progression-free survival in patients with metastatic renal cell carcinoma with no prior therapy. Overall treatment differences were evaluated in a post hoc analysis with a quality-adjusted time without symptoms or toxicity (Q-TWiST) methodology. METHODS: Each patient's overall survival was partitioned into 3 mutually exclusive health states: time with grade 3 or 4 toxicity (TOX), time without symptoms of disease or grade 3/4 toxicity of treatment, and time after tumor progression or relapse (REL). The time spent in each state was weighted by a health-state utility associated with that state and summed to calculate the Q-TWiST. A threshold utility analysis was used, and utilities were applied across the range of 0 (similar to death) to 1 (perfect health). RESULTS: A total of 1110 patients were enrolled (557 on pazopanib and 553 on sunitinib). The mean TOX was 31 days (95% confidence interval, 13-48 days) longer for sunitinib versus pazopanib. In the threshold utility analysis, the difference in the Q-TWiST ranged from -11 days (utility for TOX, 1; utility for REL, 0) to 43 days (utility for TOX, 0; utility for REL, 1) in favor of pazopanib across most utility combinations. Differences were significant in less than half of the utility combinations examined, and this typically occurred when the utility for TOX was lower than the utility for REL. CONCLUSIONS: Patients randomized to pazopanib had a slightly longer Q-TWiST in comparison with sunitinib patients, and this was primarily due to the reduced length of TOX.