The FDA has approved the combination of belzutifan (Welireg) and pembrolizumab (Keytruda) as adjuvant treatment for patients with high-risk clear cell renal cell carcinoma (ccRCC) after surgery, establishing a new standard of care.
The approval is based on the phase 3 LITESPARK-022 trial, which showed the combination reduced the risk of cancer recurrence or death by 28% compared with pembrolizumab alone. The benefit appeared within three months and continued even after the one-year treatment period ended.
Although the combination caused more side effects than pembrolizumab alone, the safety profile was manageable with no unexpected toxicities. The most common side effects were anemia, fatigue, and low blood oxygen levels. Treatment discontinuation due to side effects occurred in 10.2% of patients receiving the combination versus 7.3% with pembrolizumab alone.
Researchers are now studying biomarkers and circulating tumor DNA (ctDNA) to identify which patients are most likely to benefit from this dual therapy.