Dr Powles on Results from a Q-TWiST Analysis of Belzutifan vs Everolimus in Previously Treated Advanced RCC

"[These data do] support the use of [belzutifan] in pretreated patients. In my clinical practice—for example, I may give, let's say, axitinib plus pembrolizumab first…[then] cabozantinib second. And [belzutifan], for me, will be an attractive third-line agent, rather than switching to another VEGF TKI, which may be associated with chronic toxicity."

Thomas Powles, MD, professor of genitourinary oncology and director of Barts Cancer Centre in London, discussed results from a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of belzutifan (Welireg) vs everolimus (Afinitor) in patients with previously treated advanced renal cell carcinoma (RCC). Findings from the phase 3 LITESPARK-005 trial (NCT04195750) showed a statistically significant and clinically meaningful improvement for patients treated with belzutifan compared with everolimus.

LITESPARK-005 enrolled patients with advanced clear cell RCC who had previously received both immune checkpoint inhibitor and anti-angiogenic therapy. In this population, belzutifan demonstrated superior progression-free survival (PFS) compared with everolimus, along with a differentiated safety profile. The Q-TWiST analysis aimed to quantify the clinical benefit of belzutifan by incorporating both PFS and health-related quality-of-life metrics, Powles explained.

The Q-TWiST metric reflects the mean duration of time patients experience without disease progression and without grade 3 or higher toxicity, weighted by utility values derived from quality-of-life assessments. According to Powles, this approach offers a clinically relevant estimate of net treatment benefit by integrating both efficacy and tolerability data.

Findings from the analysis demonstrated that belzutifan conferred a longer Q-TWiST duration vs everolimus. These results align with clinical experience suggesting that belzutifan is generally well tolerated and offers a non–VEGF-based treatment alternative, which may be particularly beneficial in later-line settings where cumulative toxicity is a concern, Powles said.

He noted that the Q-TWiST benefit observed with belzutifan surpassed key thresholds used to define clinical relevance, supporting its role in the post–VEGF TKI and post-IO treatment setting. In practice, he said, belzutifan may represent an attractive third-line option following initial treatment with an IO/TKI combination and a subsequent