Health-related quality-of-life outcomes from a phase II open-label trial of two different starting doses of lenvatinib in combination with everolimus for treatment of renal cell carcinoma following one prior VEGF-targeted treatment.

Abstract

314 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer, constituting 80% to 85% of primary renal neoplasms. Preserving health-related quality of life (HRQOL) is an important goal during RCC treatment, but HRQOL analyses in prospective clinical trials in RCC are limited. We report changes in HRQOL, a secondary endpoint of this phase II trial. Methods: HRQOL data were collected during a multicenter, randomized, open-label phase II study comparing the safety and efficacy of two different starting doses of lenvatinib (18 mg vs. 14 mg daily [QD]) in combination with everolimus (5 mg QD), following one prior vascular endothelial growth factor–targeted treatment (NCT03173560). HRQOL was measured using three different instruments, including the FKSI-DRS, EORTC QLQ-C30, and EQ-5D-3L. Change from baseline HRQOL was assessed using linear mixed-effects models. Deterioration events for time to deterioration (TTD) analyses were defined using established thresholds for minimally important differences in the change from baseline for each scale (i.e., 10 points for EORTC, 3 points for FKSI-DRS, 0.08 points for EQ-5D index, and 10 points for EQ-VAS). The distribution of TTD and median TTD for each treatment arm were estimated using the Kaplan-Meier method. Results: Baseline characteristics, including baseline scores of the 343 participants randomly assigned to 14 mg QD lenvatinib (n = 172) and 18 mg QD lenvatinib (n = 171), were well balanced. The average scores for the 18 mg QD group were generally higher, with lower symptom severity than the 14 mg QD group. The least squares mean estimates for change from baseline were favorable for the 18 mg QD group over the 14 mg QD group for the FKSI-DRS and most EORTC QLQ-C30 scales; however, the differences between treatments did not exceed the minimally important difference for clinical significance. Both study arms showed an increase diarrhea severity. Median TTD was longer among participants in the 18 mg QD group than those in the 14 mg QD group for most scales. Conclusions: In most scales, participants who received an 18 mg QD lenvatinib starting dose had better HRQOL and longer time to deterioration than those who received a 14 mg QD starting dose. These findings suggest that the approved treatment regimen of an 18 mg starting dose of lenvatinib in combination with everolimus remains favorable for RCC treatment, following one prior vascular endothelial growth factor–targeted treatment. Clinical trial information: NCT03173560 .