Belzutifan Plus Lenvatinib vs Cabozantinib in RCC: PRO Highlights From LITESPARK-011
- Time to deterioration in FKSI-DRS and QLQ-C30 GHS/QoL scores was similar between the 2 arms.
- LSM and empirical mean score changes remained generally comparable through week 108, apart from a marked, clinically meaningful worsening in the QLQ-C30 diarrhea scale with cabozantinib.
- PRO completion declined to approximately 59% of patients by week 45, though compliance among those expected to complete assessments remained high (89%-94%).
How was LITESPARK-011 designed?
LITESPARK-011 was a randomized, open-label, study that enrolled patients with unresectable, locally advanced, or metastatic clear cell RCC and a Karnofsky performance status of 70% or higher who had received up to 2 prior systemic regimens.¹ Eligible patients had progressed on or after anti–PD-(L)1 monoclonal antibody therapy given as first- or second-line treatment, or within 6 months of the last dose of adjuvant anti–PD-(L)1 therapy; prior VEGFR-TKI therapy was permitted.
Patients were randomly assigned 1:1 to belzutifan at 120 mg orally once daily plus lenvatinib at 20 mg orally once daily (n = 371) or cabozantinib at 60 mg orally once daily (n = 376), stratified by IMDC prognostic score, line of prior anti–PD-(L)1 therapy, and geographic region.
The dual primary end points were PFS per RECIST 1.1 criteria by blinded independent central review and overall survival, with ORR as a key secondary end point. PROs were assessed as an exploratory end point using the FKSI-DRS and EORTC QLQ-C30 instruments.
Treatment differences were estimated using least squares mean (LSM) score change from baseline via a constrained longitudinal data analysis model, with PRO score as the response variable and treatment-by-time interaction and stratification factors as covariates; PRO analyses were descriptive and not formally statistically tested. The PRO analysis population comprised all randomly assigned patients who received at least 1 dose of study treatment and completed at least 1 PRO assessment (belzutifan plus lenvatinib, n = 365; cabozantinib, n = 366).
What additional symptom and functioning data were reported?
At a median follow-up of 29.0 months (range, 19.3-49.2) from a data cutoff of April 9, 2025, LSM score changes from baseline to week 45 across EORTC QLQ-C30 functional domains (GHS/QoL, physical, role, emotional, cognitive, and social functioning) and most symptom domains (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, and financial difficulties) were generally similar between the belzutifan plus lenvatinib and cabozantinib arms. The exception was the QLQ-C30 diarrhea scale, which showed a marked and clinically meaningful worsening with cabozantinib relative to the combination arm.
Empirical mean score changes from baseline in FKSI-DRS and GHS/QoL scores tracked closely between arms out to week 108 and remained generally stable over time for both regimens. Time to deterioration in QLQ-C30 physical functioning (HR, 1.13; 95% CI, 0.91-1.40) and role functioning (HR, 1.10; 95% CI, 0.90-1.35) also did not differ meaningfully between arms.
What were the limitations of the PRO analysis?
Questionnaire completion rates declined over the course of the study, falling to approximately 59% by week 45 for both FKSI-DRS and QLQ-C30 in each arm, although compliance among patients still expected to complete assessments remained high (89.2%-93.9%). The investigators noted that informative missingness related to disease progression, treatment discontinuation, adverse events, or death should be considered when interpreting long-term PRO findings. PRO comparisons were descriptive only and not formally tested for statistical significance.
“Together with the previously reported efficacy [superior PFS and ORR] and safety results, these findings further support belzutifan plus lenvatinib as a promising new treatment option for patients with advanced RCC following anti–PD-(L) therapy,” Schmidinger and her coauthors wrote in their conclusion.
References
- Schmidinger M, Heng DYC, McDermott R, et al. Belzutifan plus lenvatinib versus cabozantinib in post–PD-(L)1 renal cell carcinoma: health-related quality-of-life outcomes in the phase 3 LITESPARK-011 study. Presented at: Kidney Cancer Research Summit; July 23-24, 2026; Boston, MA.
- Motzer RJ, McDermott R, Park SH, et al. Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial. Lancet. 2026;408(10557):808-820. doi:10.1016/S0140-6736(26)01089-5
