FDA approves belzutifan for advanced renal cell carcinoma
Regulatory approval: On Dec 14, 2023, the FDA approved belzutifan (Welireg; Merck) for patients with advanced renal cell carcinoma following prior PD-1/PD-L1 inhibitor and a VEGF tyrosine kinase inhibitor. The decision was supported by LITESPARK-005, which showed a statistically significant progression-free survival benefit versus everolimus (HR 0.75; 95% CI 0.63–0.90; 1-sided p=0.0008). Overall survival was immature at the time of analysis.
FDA approval (Dec 14, 2023)
The US Food and Drug Administration (FDA) approved belzutifan (Welireg, Merck & Co., Inc.) for patients with advanced renal cell carcinoma (RCC) after treatment with a PD-1/PD-L1 inhibitor and a VEGF tyrosine kinase inhibitor (VEGF-TKI).
Supporting evidence: LITESPARK-005
Efficacy was evaluated in LITESPARK-005 (NCT04195750), an open-label, randomized, head-to-head trial in 746 patients with unresectable locally advanced or metastatic clear cell RCC that had progressed after both a PD-1/PD-L1 checkpoint inhibitor and a VEGF-TKI. Patients were randomized 1:1 to belzutifan 120 mg once daily or everolimus 10 mg once daily, stratified by IMDC risk and number of prior VEGF-TKIs.
Major endpoints were progression-free survival (PFS) by blinded independent central review and overall survival (OS).
Belzutifan demonstrated a statistically significant PFS improvement vs everolimus (HR 0.75, 95% CI 0.63–0.90; 1-sided p=0.0008). Median PFS was 5.6 months in both arms (belzutifan 95% CI 3.9–7.0; everolimus 95% CI 4.8–5.8), with Kaplan–Meier curves indicating non-proportional hazards. OS was immature (59% deaths), with no trend toward detriment reported.
Safety and dosing
Common adverse reactions (≥25%) included decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased ALT, decreased sodium, increased potassium, and increased AST. Recommended dose: 120 mg orally once daily until progression or unacceptable toxicity.
The application received priority review.