Q-TWiST Analysis Builds on LITESPARK-005 Efficacy of Belzutifan in ccRCC

The enhanced tolerability of belzutifan (Welireg) in patients with clear cell renal cell carcinoma (ccRCC) compared with everolimus (Afinitor) could make it an attractive option for this patient group, according to Thomas Powles, MBBS, MCRP, MD.

Results from the quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of the phase 3 LITESPARK-005 trial (NCT04195750) showed the mean Q-TWiST of 17.47 months in the belzutifan arm and 14.81 months in the everolimus) arm.

The sensitivity analysis assessed grade 1 to 4 serious adverse effects with a mean Q-TWiST of 17.50 months vs 15.03 months in the belzutifan vs everolimus arms, respectively. There was a Q-TWiST gain of 10.50% in this analysis.

CancerNetwork® spoke with Powles, a professor of genitourinary oncology, lead for Solid Tumor Research, and director of Barts Cancer Institute at St. Bartholomew’s Hospital, Queen Mary University of London, regarding these results he presented at the 2025 Kidney Cancer Research Summit (KCRS).

Transcript:

The story behind belzutifan, so far, is an agent that has been developed in 2 areas that are contrasting with each other. No. 1 is VHL-driven disease, and that disease has shown that renal tumors can be put into remission regression associated with belzutifan, preventing surgery on primary renal tumors. That’s important for patients. In the other extreme, in metastatic clear cell renal cancer, we go all the way where it’s been developed very late, third or fourth line, in many cases. Those 2 are very different from each other. The development of the disease, the VHL disease, and how that relates to patients who are very heavily pre-treated, is quite complicated. It’s probable, or even likely, that if we use belzutifan earlier in the disease process, it will work better. What we've shown with this Q-TWiST analysis is not only that it is more active than everolimus, but it appears to be, from a quality-of-life perspective, and a time-dependent quality of life analysis, to be better tolerated, making it an attractive [option].

Reference

Powles T, de Velasco G, Choueiri TK, et al. Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of belzutifan versus everolimus in previously treated advanced renal cell carcinoma (RCC): LITESPARK-005 (LS-005). Presented at the 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA. Abstract 13.