Welireg Improves Quality-Adjusted Survival Time in Advanced RCC

Welireg improved quality-adjusted survival time versus Afinitor in advanced renal cell carcinoma, extending progression-free survival and reducing side effects.

Welireg (belzutifan) improved quality-adjusted survival time significantly over Afinitor (everolimus) in patients with advanced renal cell carcinoma, according to a quality-adjusted time without symptoms or toxicity analysis from the phase 3 LITESPARK-005 trial presented at the 2025 Kidney Cancer Research Summit. This finding highlights Welireg’s potential to extend survival while reducing side effects for patients with advanced kidney cancer.

Based on the main analysis, in which toxicity accounted for grade 3 (severe)/4 (life-threatening) side effects, the mean Q-TWiST was 17.47 months among patients who received Welireg (374 patients) versus 14.81 months among those who received Afinitor (372 patients). The relative gain in Q-TWiST with Welireg, defined as the absolute Q-TWiST difference divided by mean overall survival (OS) for the Afinitor arm, was 11.32% in the main analysis.

The sensitivity analysis, which included grade 1 (mild) to 4 serious side effects, showed a mean Q-TWiST of 17.50 months in the Welireg arm versus 15.03 months in the Afinitor arm. Data highlighted a relative Q-TWiST gain of 10.50% in the sensitivity analysis.

“In conclusion, Welireg outperformed Afinitor from a response and a progression-free-survival [PFS] perspective. The toxicity profile was distinct, the quality of life was better, and so was the TWiST and the Q-TWiST analysis,” lead study investigator, Dr. Thomas Powles stated in the presentation. “This [Q-TWiST analysis] does help patients and doctors make decisions. I quite like this type of exploratory analysis, and I'm happy to be involved in future projects with it.”

Powles is 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.

As part of this analysis, investigators divided patient survival time following randomization into three mutually exclusive states: investigator-assessed time with grade 3/4 toxicity before disease progression (TOX), time without symptoms and progression of grade 3/4 toxicity (TWiST), and time from progression until death (REL). Investigators calculated Q-TWiST as the sum-product of restricted mean time spent in the individual states and state-specific utility weights. Additionally, standard utility weights used in literature — one for TWiST as well as 0.5 for TOX and REL — were considered, and threshold utility analysis was performed to determine the impact of the differing health state utility.

The study authors summarized the treatment effects as differences in restricted mean time spent in each state; the difference in Q-TWiST; and the relative gain in Q-TWiST, or the absolute Q-TWiST difference divided by mean OS in the Afinitor arm. Use of nonparametric bootstrapping method was involved for generating 95% confidence intervals for the treatment differences related to the health states and Q-TWiST.

In the multicenter, open-label phase 3 LITESPARK-005 trial, patients were randomly assigned 1:1 to receive Welireg at 120 milligrams (mg) or Afinitor at 10 mg orally once daily until progressive disease or unacceptable toxicity.

The trial’s dual primary end points were PFS and OS. Secondary end points included the objective response rate, duration of response and safety.

In the main analysis, the mean TOX time was 1.45 months in the Welireg arm versus 1.22 months in the Afinitor arm. Despite a numerically longer time in TOX among those in the Welireg arm, data showed significantly longer time in TWiST with Welireg at a mean of 10.73 months versus 6.07 months with Afinitor, which was driven by prolonged periods without progression.

Prior safety data showed that the most common any-grade side effects in the Welireg and Afinitor arms, respectively, included anemia (83.1% versus 57.2%), fatigue (32.3% versus 25.8%), nausea (18.5% versus 12.2%), edema peripheral (17.2% versus 18.1%), and constipation (16.9% versus 8.3%).

References

1. “Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of Welireg versus Afinitor in previously treated advanced renal cell carcinoma” by Dr. Powles, et al., Presented at the 2025 Kidney Cancer Research Summit.
2. “Welireg versus Afinitor for advanced renal cell carcinoma” by Dr. Choueiri, et al., New England Journal of Medicine.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.