OBJECTIVES: To evaluate if quality-adjusted survival for temsirolimus (TEMSR) met criteria for minimal clinically important difference (MCID) in a randomized, outpatient study of first-line treatment of patients with poor-prognosis, advanced renal cell carcinoma (RCC). In this study TEMSR (25 mg IV once-weekly) was associated with median 10.9 months overall survival (OS) compared with median 7.3 months OS for interferon (IFN) (up to 18 MU subcutaneously thrice weekly (p=0.008). METHODS: OS was partitioned into 3 distinct periods: a) time in serious toxicity (aggregated time in grade 3 or 4 adverse events (AEs); b) time in progression (based on tumor response assessment); and c) time without symptoms of progression or toxicity (TWiST). Based on patient-reported responses to the EuroQol (EQ-5D) at representative time points during each period, Q-TWiST was estimated as the measure of quality-adjusted survival. Treatment group differences in Q-TWiST were evaluated in terms of restricted means, with patient follow-up truncated at the median of 17.9 months. Variance and covariance were estimated using bootstrap methods. Following published literature, the clinical importance of the TEMSR-IFN difference in Q-TWIST was the percentage obtained when this difference was divided by mean OS for IFN (the control group). RESULTS: All 626 randomized patients were included in computation of health state durations. Response rates for the EQ-5D were 87% (260/300) during progression, 40% (230/570) during toxicity, and 99% (278/279) during TWiST. Patients in the TEMSR group had 1.3 months greater Q-TWiST than those in the IFN group (TEMSR=7.0 months vs. IFN=5.7 months; p=0.0015). The MCID was 14.8% (1.3 months divided by 8.8 months [IFN mean OS]), which is within the published range of 10-15% for MCID in cancer trials. CONCLUSION: Patients with advanced RCC receiving TEMSR met criteria for clinically important improvement in quality-adjusted survival.