Belzutifan plus lenvatinib versus cabozantinib in post–PD-(L)1 renal cell carcinoma (RCC): Health-related quality-of-life (HRQoL) outcomes in the phase 3 LITESPARK-011 study.

e23270 Background: Belzutifan + lenvatinib significantly improved PFS and ORR vs cabozantinib, and had manageable safety, in participants (pts) with advanced RCC that progressed on or after anti–PD-(L)1 therapy in the phase 3 LITESPARK-011 study (NCT04586231). We report HRQoL outcomes from LITESPARK-011. Methods: Adults (≥18 y) with advanced RCC that progressed on or after anti–PD-(L)1 therapy as the immediate prior treatment were randomly assigned 1:1 to receive belzutifan 120 mg + lenvatinib 20 mg PO QD or cabozantinib 60 mg PO QD. HRQoL was evaluated in pts who received ≥1 dose of study treatment and completed ≥1 patient-reported outcome (PRO). Prespecified exploratory end points included time to deterioration (TTD) and least squares mean (LSM) change from baseline in FKSI-DRS, and EORTC QLQ-C30 global health status/quality of life (GHS/QoL), physical functioning (PF), and role functioning (RF) subscales. Questionnaires were completed electronically on day 1 of wk 1, 3, 5, and 9, Q4W thereafter, at treatment discontinuation, and 30 days after last dose. The analysis timepoint was wk 45 (last timepoint where completion and compliance rates of ~60% and ≥80%, respectively, were observed). PROs were not formally statistically tested. Results: The PRO analysis population included 731 pts (n = 365, belzutifan + lenvatinib; n = 366, cabozantinib). At data cutoff (Apr 9, 2025), median study follow-up was 29.0 mo (range, 19.3-49.2). Completion rates for FKSI-DRS and QLQ-C30 were > 85% at baseline (compliance > 86%) and > 55% at wk 45 (compliance > 89%) in each arm. TTD and LSM change from baseline in FKSI-DRS, QLQ-C30 GHS/QoL, PF, and RF scores were similar between arms (Table). Conclusions: Belzutifan + lenvatinib had similar TTD for FKSI-DRS, and GHS/QoL, PF, and RF vs cabozantinib. LSM changes in HRQoL and disease-specific symptoms from baseline to wk 45 were also similar for both arms. Combined with efficacy and safety data, results support belzutifan + lenvatinib as a new treatment option for advanced RCC that progressed after anti–PD-(L)1 therapy. Clinical trial information: NCT04586231 . Median TTD, mo(95% CI) Median TTD, mo(95% CI) LSM change from baseline (95% CI) LSM change from baseline (95% CI) Belzutifan + lenvatinib Cabozantinib Belzutifan + lenvatinib Cabozantinib FKSI-DRS 13.8 (6.4-20.3) 10.6 (7.4-20.2) −0.05 (−0.57-0.48) −0.23 (−0.75-0.30) HR 1.02 (95% CI, 0.82-1.28) - Difference 0.18 (95% CI, −0.51-0.87) - QLQ-C30 GHS/QoL 7.9 (5.5 to 13.1) 10.1 (6.5-19.3) −4.13 (−6.39-−1.87) −4.35 (−6.60-−2.11) HR 1.07 (95% CI, 0.86-1.34) - Difference 0.23 (95% CI, −2.70-3.15) - QLQ-C30 PF 7.9 (5.5-13.8) 11.6 (6.9-16.6) −5.66 (−7.78-−3.55) −3.96 (−6.06-−1.86) HR 1.13 (95% CI, 0.91-1.40) - Difference −1.70 (95% CI, −4.58-1.17) - QLQ-C30 RF 3.7 (2.8 to 6.5) 6.4 (4.6-8.2) −5.62 (−8.61-−2.63) −6.96 (−9.93-−3.98) HR 1.10 (95% CI, 0.90-1.35) - Difference 1.34 (95% CI, −2.59-5.26) -