On December 14, the U.S. Food and Drug Administration (FDA) approved belzutifan (Welireg) for patients with advanced renal cell carcinoma following treatment with a PD-1 or PD-L1 inhibitor and a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor.
LITESPARK-005
Efficacy was evaluated in LITESPARK-005 (ClinicalTrials.gov identifier NCT04195750), an open-label, randomized, head-to-head trial of 746 patients with unresectable locally advanced or metastatic clear cell renal cell carcinoma that had progressed after both a PD-1 or PD-L1 checkpoint inhibitor and a VEGF tyrosine kinase inhibitor. Patients were randomly assigned 1:1 to receive 120 mg of belzutifan or 10 mg of everolimus once daily. Random assignment was stratified by International Metastatic RCC Database Consortium risk category and number of prior VEGF tyrosine kinase inhibitors.
The major efficacy outcome measures were progression-free survival (assessed by blinded independent central review) and overall survival.
A statistically significant improvement in progression-free survival was demonstrated for belzutifan compared with everolimus, with a hazard ratio of 0.75 (95% confidence interval [CI] = 0.63–0.90, one-sided P = .0008). Kaplan-Meier curves reflected nonproportional hazards with similar median progression-free survival estimates of 5.6 months (95% CI = 3.9–7.0 months) in the belzutifan arm and 5.6 months (95% CI = 4.8–5.8 months) for those receiving everolimus. Although overall survival results were immature at the time of the current analysis, with 59% of deaths reported, no trend toward a detriment was observed. A descriptive analysis of patient-reported symptoms and functional outcomes was supportive of improved tolerability for belzutifan compared with everolimus.
The most common adverse reactions (occurring in ≥ 25% of patients receiving belzutifan) were decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased alanine aminotransferase, decreased sodium, increased potassium, and increased aspartate aminotransferase.
The recommended belzutifan dose is 120 mg administered orally once daily until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review.
