Improving HRQoL Correlates With Longer PFS/OS in LITESPARK-005

Belzutifan is an oral hypoxia-inducible factor-2α (HIF-2α) inhibitor compared with everolimus (mTOR inhibitor) in the randomized Phase 3 LITESPARK-005 trial (NCT04195750) in previously treated advanced clear cell RCC after an immune checkpoint inhibitor and antiangiogenic therapy; this post hoc PRO analysis included 720 treated patients with ≥1 FKSI-DRS and/or EORTC QLQ-C30 GHS/QoL assessment (belzutifan n=366; everolimus n=354; median follow-up 35.8 months). Higher baseline FKSI-DRS was modestly prognostic for better PFS (HR 0.91; 95% CI 0.86-0.96) and OS (HR 0.86; 95% CI 0.81-0.91), and longitudinal improvements in FKSI-DRS and QLQ-C30 were strongly associated with lower risk of progression (both PFS HR 0.80; 95% CI 0.74-0.85) and death (OS HR 0.57 for FKSI-DRS; 0.64 for QLQ-C30); landmark “stable/improved vs deteriorated” HRs favored stable/improved HRQoL at weeks 13/25/53 (e.g., week 13 OS HR 0.52 for FKSI-DRS; 0.53 for QLQ-C30). While this abstract is not re-reporting the parent efficacy readout, it’s worth anchoring that the underlying LITESPARK-005 efficacy benefit vs everolimus was mainly in ORR (≈22% vs ≈3%-4%) and a PFS HR 0.75 despite similar median PFS (5.6 months in both arms)—so these PRO associations may be capturing heterogeneity in disease biology/early benefit rather than implying that “feeling better” is causal.