Belzutifan (Welireg) plus lenvatinib (Lenvima) produced patient-reported outcomes (PROs) comparable to those with cabozantinib (Cabometyx) in patients with renal cell carcinoma (RCC) that progressed after anti–PD-(L)1 therapy, according to health-related quality-of-life (HRQoL) findings from the phase 3 LITESPARK-011 study (NCT04586231) presented during the 2026 Kidney Cancer Research Summit.1
Time to confirmed deterioration in disease-related symptoms per the Functional Assessment of Cancer Therapy–Kidney Symptom Index–Disease-Related Symptoms (FKSI-DRS) was similar between the belzutifan plus lenvatinib and the cabozantinib arms, with median times of 13.8 months (95% CI, 6.4-20.3) and 10.6 months (95% CI, 7.4-20.2), respecitively (HR, 1.02; 95% CI, 0.82-1.28). Time to deterioration in global health status/quality of life (GHS/QoL) per the EORTC QLQ-C30 was also comparable between arms (HR, 1.07; 95% CI, 0.86-1.34).
The findings build on previously reported efficacy data from LITESPARK-011 showing superior progression-free survival (PFS) and objective response rate (ORR) with belzutifan plus lenvatinib vs cabozantinib in this population.2
“Patient-reported outcomes were generally comparable between treatment arms and showed no additional HRQoL burden with belzutifan plus lenvatinib,” Manuela Schmidinger, MD, the director of the Kidney Cancer Program at the Medical University of Vienna in Austria, and her coauthors wrote in a poster presentation of the data.
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
