OBJECTIVE: Few studies have measured preference-based utility weights as evaluation of health-related quality of life under specific first-line treatments for advanced renal cell carcinoma (aRCC). This study assessed health state utilities and adverse event (AE)-related disutility among previously untreated patients with aRCC randomized to pembrolizumab/axitinib or sunitinib in a multinational phase III trial (KEYNOTE-426/NCT02853331).

METHODS: In KEYNOTE-426, patients completed the EuroQoL-Five Dimensions-Three Levels questionnaire (EQ-5D-3L) at 3- to 12-week intervals during study treatment until discontinuation and at 30 days post-discontinuation. A linear mixed-effects regression model was fitted using repeated measures data from patient-visits in which both disease progression status (per Response Evaluation Criteria in Solid Tumors V1.1 criteria) and EQ-5D-3L were available (N=810 patients with 7,119 patient-visits). The dependent variable was EQ-5D-3L utility (United Kingdom valuation). Independent variables included indicators for health state (progression-free vs. progressive disease) and presence/absence of any grade 3+ AE. Patient-level random effects were included to account for within-subject correlation. In a sensitivity analysis, a treatment group indicator was added to the regression to derive treatment-specific utilities.

RESULTS: In the absence of grade 3+ AEs, health state utilities (pooled across treatment arms) were estimated to be 0.8033 (standard error=0.0067) for pre-progression vs. 0.7724 (0.0090) for progressive disease (p<0.001). Presence of any grade 3+ AE corresponded to an additive disutility of -0.0405 (0.0058) (p<0.001). In the sensitivity analysis, treatment-specific utilities for pre-progression vs. progressive disease were 0.8115 (0.0091) vs. 0.7805 (0.0109) for pembrolizumab/axitinib, and 0.7946 (0.0094) vs. 0.7637 (0.0112) for sunitinib; AE-related disutility from this model was -0.0404 (0.0058).

CONCLUSIONS: This study obtained utilities for aRCC health states both with and without differentiation by specific first-line treatment received. Under both approaches, utility significantly worsened during grade 3+ AEs and after disease progression. These utilities can be incorporated into cost-effectiveness analyses of approved and investigational treatments for RCC.