FDA Approves Belzutifan for Patients With Advanced Renal Cell Carcinoma

The US Food and Drug Administration (FDA) has approved belzutifan for treating patients with advanced renal cell carcinoma (RCC) after they have received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). The approval of the oral treatment stems from results from the open-label, randomized head-to-head trial LITESPARK-005.

The trial included 746 patients with unresectable locally advanced or metastatic clear cell RCC whose cancer had progressed after receiving a PD-1 or PD-L1 checkpoint inhibitor and a VEGF-TKI. The participants were randomized at a 1:1 ratio, which was stratified by International Metastatic RCC Database Consortium risk category and number of prior VEGF-TKI. Patients were administered 120 mg belzutifan or 10 mg everolimus once per day. The main outcome measures of the trial were progression-free survival (PFS) and overall survival (OS).

The results showed that there was a statistically significant improvement in PFS for patients who received belzutifan compared to those who received everolimus (hazard ratio [HR] 0.75 [(95% CI: 0.63, 0.90); 1-sided P = .0008]). According to the Kaplan-Meier curves, non-proportional hazards for both the belzutifan treatment arm and the everolimus arm had similar median PFS estimates of 5.6 months (95% CI: 3.9, 7.0) and 5.6 months (95% CI: 4.8, 5.8), respectively. For the OS, although the data were immature at the time of analysis, the results point toward a positive trend in survival. In addition, patient-reported symptom and functional outcomes demonstrated better tolerability of belzutifan vs everolimus among the patients.

The most common adverse reactions occurred in ≥25% patients who received belzutifan and included decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased alanine aminotransferase, decreased sodium, increased potassium, and increased aspartate aminotransferase. The FDA notes that the recommended dose for belzutifan is 120 mg and it should be administered orally once per day until disease progression or unacceptable toxicity occurs.

FDA. FDA approves belzutifan for advanced renal cell carcinoma. December 14, 2023. Accessed January 9, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-advanced-renal-cell-carcinoma