Better patient-reported outcomes with belzutifan versus everolimus in previously treated advanced renal cell carcinoma

Patients with advanced renal cell cancer (RCC) whose cancer progresses after both immune checkpoint and anti-angiogenic therapies have limited treatment options at their disposal. In the LITESPARK-005 study, belzutifan showed superior efficacy versus everolimus in previously treated patients with advanced RCC.  Results from a patient-reported outcome analysis now also indicate better disease-specific symptoms and quality of life with belzutifan compared with everolimus in patients with advanced clear-cell RCC.

Belzutifan is a first-in-class, oral hypoxia-inducible factor-2 alpha inhibitor. Previously, the randomised, phase III LITESPARK-005 study demonstrated significant improvements in progression-free survival (PFS) and objective response rate (ORR) with belzutifan vs. everolimus in patients with advanced clear cell renal cell carcinoma (RCC) after prior immune checkpoint and anti-angiogenic therapies. At ASCO GU 2024, Dr. Powles presented the patient-reported outcomes (PROs) for belzutifan vs. everolimus in LITESPARK-005.

Methods

LITESPARK-005 is a randomised, open-label phase III study evaluating belzutifan (120 mg orally once daily) compared with everolimus (10 mg orally once daily) for the treatment of patients with advanced RCC that has progressed after both immune checkpoint and anti-angiogenic therapies. Patient-reported outcomes were evaluated by the Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) and the EORTC Quality of Life (EORTC QLQ-C30) questionnaires in all randomised patients who received ≥1 dose of study treatment and completed ≥1 patient-reported outcome assessment. Questionnaires were administered electronically on day 1 of week 1, 3, 5, and 9, every 4 weeks thereafter, at treatment discontinuation, and on day 30 after the last dose. Prespecified secondary endpoints were the time to deterioration (TTD) and the least square (LS) mean change from baseline as measured by FKSI-DRS and QLQ-C30 global health status/quality of life (GHS/QoL) and physical functioning (PF) scales.

Results

The data cut-off date for this second prespecified interim analysis was June 13, 2023. Median follow-up was 25.7 months and the median duration of treatment was 7.6 months for patients treated with belzutifan versus 3.9 months for those who received everolimus. In total, 366 of 374 patients randomised to receive belzutifan and 354 of 372 patients randomised to receive everolimus were included in the PRO analysis population. Completion rates for the FKSI-DRS and QLQ-C30 questionnaires were >90% at baseline and >55% at week 17 in each treatment arm. The TTD in FKSI-DRS scores (not reached vs. 11.99 months; HR [95% CI]: 0.53 [0.41-0.69], p< 0.0001) and QLQ-C30 GHS/QoL scores (19.35 vs. 10.19 months; HR [95% CI]: 0.75 [0.58-0.96], p= 0.0185) were significantly longer for patients treated with belzutifan, compared with everolimus. FKSI-DRS scores and QLQ-C30 GHS/QoL scores remained fairly stable from baseline to week 17 in patients treated with belzutifan (LS mean change [95% CI]: -0.17 [-0.70-0.36] and 0.28 [-1.98-2.53], respectively) and worsened in those who received everolimus (LS mean change [95% CI]: -1.62 [-2.17 to -1.06] and -6.11 [-8.51 to -3.70], respectively). Finally, patients treated with belzutifan showed less worsening in QLQ-C30 PF scores than those who received everolimus (LS mean change [95% CI]: -4.75 [-6.87 to -2.63] vs. -7.22 [-9.47 to -4.98]).

Conclusions

In the phase III LITESPARK-005 study, treatment with belzutifan versus everolimus resulted in a longer TTD in FKSI-DRS and EORTC QLQ-C30 scores in patients with previously treated advanced RCC. Changes in FKSI-DRS, QLQ-C30 GHS/QoL, and QLQ-C30 PF scores from baseline to week 17 also favoured belzutifan over everolimus. In conclusion, the current analysis of patient-reported outcomes indicate better disease-specific symptom control and quality of life among patients who received belzutifan, compared with everolimus.

Reference

Powles T, et al. Belzutifan versus everolimus in participants (pts) with previously treated advanced renal cell carcinoma (RCC): patient-reported outcomes (PROs) in the phase 3 LITESPARK-005 study. Presented at ASCO GU 2024; Abstract 361.