The New England Journal of MedicineBelzutifan versus Everolimus for Advanced Renal-Cell Carcinoma

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A phase 3 trial compared belzutifan, a hypoxia-inducible factor 2α inhibitor, with everolimus in patients with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies. The study evaluated progression-free survival, overall survival, and objective response rates.

Study Design:

• Multicenter, open-label, active-controlled trial
• 746 participants randomized 1:1 to receive belzutifan (120 mg) or everolimus (10 mg) orally once daily
• Treatment continued until disease progression or unacceptable toxicity
• Dual primary endpoints: progression-free survival and overall survival
• Key secondary endpoint: objective response rate

Key Findings:

• Median progression-free survival: 5.6 months for both groups
• 18-month progression-free survival: 24.0% (belzutifan) vs. 8.3% (everolimus) (P=0.002)
• Objective response rate: 21.9% (belzutifan) vs. 3.5% (everolimus) (P<0.001)
• Median overall survival: 21.4 months (belzutifan) vs. 18.1 months (everolimus) (P=0.20, not statistically significant)
• Grade 3 or higher adverse events: 61.8% (belzutifan) vs. 62.5% (everolimus)
• Treatment discontinuation due to adverse events: 5.9% (belzutifan) vs. 14.7% (everolimus)

HCN Medical Memo
Although belzutifan showed promising results in progression-free survival and objective response rates, the lack of statistically significant improvement in overall survival warrants further investigation. Physicians should consider the potential benefits and risks when discussing eventual treatment options with patients who have previously received immune checkpoint and antiangiogenic therapies for advanced clear-cell renal-cell carcinoma.

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