FDA Approves Belzutifan in Advanced RCC

Results from the phase 3 LITESPARK-005 trial led to the approval of belzutifan for patients with advanced renal cell carcinoma, according to the FDA.

The FDA has approved belzutifan (Welireg) for patients with advanced renal cell carcinoma (RCC) after a PD-L1/PD-1 inhibitor and VEGF tyrosine kinase inhibitor (TKI) for patients with advanced renal cell carcinoma (RCC), according to a press release from the organization.

The approval is based on results from the phase 3 LITESPARK-005 (NCT04195750) trial which analyzed belzutifan compared with everolimus (Afinitor) for patients with advanced or metastatic clear cell RCC. In the trial, patients received belzutifan at 120 mg vs everolimus at 10 mg dailyeach day.

A statistically significant progression-free survival (PFS) was observed in the belzutifan arm vs everolimus (HR, 0.75; 95% CI, 0.63-0.90; 1-sided P = .0008). When the Kaplan-Meier curves were assessed, there were non-proportional hazards between the belzutifan arm at 5.6 months (95% CI, 3.9-7.0) vs the everolimus arm (95% CI, 4.8-5.8).

Currently, the overall survival (OS) results are still immature at the current time of the analysis. Investigators reported 59% of patients died, and there was no trend towards a detriment.

Common adverse effects observed in more than 25% of patients included decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, decreased lymphocytes, increased alanine aminotransferase, decreased sodium, increased potassium, and increased aspartate aminotransferase.

The trial enrolled 746 patients who were randomly assigned 1:1 to either the experimental or control arm. The primary end point was PFS via RECIST v1.1 and assessed by blinded independent central review, as well as OS. Secondary end points included objective response rate per RECIST v1.1. and duration of response.

Patients were stratified based on the International Metastatic RCC Database Consortium risk category and the number of prior VEGEF-TKIs. The current recommended dose of belzutifan isn 120 mg and is to be taken until disease progression or unacceptable toxicity.

Patients were eligible for treatment if they had advanced or metastatic clear cell RCC, disease progression on or after having received systemic therapy for locally advanced or metastatic RCC, received no more than 3 prior lines of therapy, and haves adequate organ function.

Exclusion criteria included having a known additional progressive malignancy with required treatment during the last 3 years, known central nervous system metastases and/or carcinomatous meningitis, or haavings clinically significant cardiac disease.

Reference

FDA approves belzutifan for advanced renal cell carcinoma. News release. FDA. December 14, 2023. Accessed December 14, 2023. https://bit.ly/3NuRveV