Belzutifan (HIF-2α inhibitor) + lenvatinib holds HRQoL steady vs cabozantinib in post–PD-(L)1 RCC

Belzutifan (a first-in-class oral HIF-2α inhibitor) plus lenvatinib (a VEGFR/FGFR multikinase TKI) was compared with cabozantinib (VEGFR/MET/AXL TKI) in the open-label Phase 3 LITESPARK-011 trial (NCT04586231) in advanced RCC progressing on/after anti–PD-(L)1 therapy as the immediate prior regimen; HRQoL analyses included 731 treated patients with ≥1 PRO (n=365 vs 366), with data cutoff April 9, 2025 and median follow-up 29.0 months. At the week-45 analysis timepoint, time to deterioration and least-squares mean change from baseline were broadly similar between arms across FKSI-DRS (median TTD 13.8 vs 10.6 months; HR 1.02) and EORTC QLQ-C30 domains including GHS/QoL (7.9 vs 10.1 months; HR 1.07), physical functioning (7.9 vs 11.6 months; HR 1.13), and role functioning (3.7 vs 6.4 months; HR 1.10), with small between-arm differences in change scores (all CIs crossing 0). This “no HRQoL penalty” sits alongside the previously reported efficacy win for belzutifan+lenvatinib vs cabozantinib in this setting (median PFS 14.8 vs 10.7 months; HR 0.70; ORR 52.6% reported for the combo), while noting that PROs were exploratory and not formally statistically tested.