Results from the phase 3 LITESPARK-022 trial show that adding belzutifan (Welireg) to pembrolizumab (Keytruda) significantly improves outcomes for patients with clear cell renal cell carcinoma (ccRCC) who are at high risk of recurrence after kidney removal surgery. The combination reduced the risk of cancer returning or death by 28% compared with pembrolizumab alone. At 30 months, 75.8% of patients receiving the combination remained disease-free, compared with 68.6% of those receiving pembrolizumab alone. Early overall survival results favor the combination, but the difference is not yet statistically significant. The benefit was seen across most patient subgroups.
Side effects were more common with the combination but were considered manageable. Anemia and low oxygen levels were more frequent, with anemia occurring in 84% of patients in the combination group, although severe cases were less common. Fatigue, increased liver enzymes, and dizziness were also reported more often. Despite the higher rate of side effects, the number of patients who stopped treatment due to adverse events was similar between the two groups.
Pembrolizumab has been the standard post-surgery treatment since the KEYNOTE-564 trial, but many patients still experience recurrence. LITESPARK-022 is the first phase 3 adjuvant kidney cancer study to show a clear benefit for a combination therapy compared with an active immunotherapy alone, suggesting a new potential standard for high-risk patients.