Patients with advanced renal cell carcinoma (RCC) experienced a clinically meaningful enhancement in quality-adjusted survival time when treated with belzutifan (Welireg) compared to everolimus (Afinitor), according to a recent quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis.

The study, presented at the 2025 Kidney Cancer Research Summit, revealed that belzutifan yielded a mean Q-TWiST of 17.47 months, significantly outperforming the 14.81 months observed with everolimus. This translates to a notable improvement in how patients experience life during their treatment.

“Belzutifan outperformed everolimus 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,” stated lead investigator, Thomas Powles, MBBS, MCRP, MD.

“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.”
—Thomas Powles, Professor of Genitourinary Oncology, Queen Mary University of London

The Q-TWiST metric accounts for time spent in different health states, including time with grade 3/4 adverse effects (AEs), time without symptoms or toxicity (TWiST), and time from progression to death. Standard utility weights were applied, with a higher value for TWiST indicating a better quality of life.

While the time spent with grade 3/4 toxicity was numerically longer with belzutifan, the drug demonstrated substantially longer time in the TWiST state. This was driven by extended periods without disease progression, contributing to the overall improved Q-TWiST.

The LITESPARK-005 trial, a phase 3 study, randomly assigned patients to receive either belzutifan or everolimus. Eligibility criteria included stage IV clear cell RCC, progression after prior therapies, and a Karnofsky performance status of 70 or higher.

Common AEs observed in the belzutifan arm included anemia and fatigue, while the everolimus arm also reported anemia and fatigue among the most frequent adverse events. This analysis provides valuable insights for clinicians and patients when selecting treatment for advanced RCC.

The findings align with broader trends in cancer treatment where improving patient quality of life is increasingly recognized as a crucial component of therapeutic success. For instance, in 2023, the FDA approved ipilimumab and nivolumab combination therapy for certain advanced kidney cancer patients, emphasizing durable responses and improved patient-reported outcomes.

The sensitivity analysis, which included grade 1 to 4 serious AEs, further supported belzutifan’s advantage, showing a mean Q-TWiST of 17.50 months versus 15.03 months for everolimus, representing a relative Q-TWiST gain of 10.50%.