Objective:

To evaluate the efficacy and safety of adjuvant pembrolizumab plus belzutifan compared to pembrolizumab plus placebo in patients with surgically resected clear-cell renal-cell carcinoma at increased risk for recurrence.

Approach:

• Study Design: A randomized, double-blind, multinational phase 3 trial (LITESPARK-022) involving 1,841 patients.
• Intervention: Patients received either 400 mg of intravenous pembrolizumab plus 120 mg of daily oral belzutifan or placebo for up to 1 year.
• Endpoints: Primary endpoint was investigator-assessed disease-free survival; secondary endpoints included overall survival and safety.

Key Findings:

• Higher disease-free survival was observed in the pembrolizumab plus belzutifan group (92% vs 85% at 12 months, 81% vs 74% at 24 months, and 76% vs 69% at 30 months).
• 186 patients in the pembrolizumab plus belzutifan group experienced disease recurrence or death compared to 246 in the placebo group.
• Grade 3 or higher adverse events occurred in 52% of the belzutifan group versus 30% in the placebo group.

Interpretation:

Adjuvant pembrolizumab plus belzutifan resulted in improved disease-free survival compared to pembrolizumab plus placebo, but overall survival data were immature at the interim analysis.

Limitations:

• Small subgroup sample sizes may limit interpretation.
• Underrepresentation of Black patients affects generalizability of the findings.

Conclusion:

Adjuvant pembrolizumab plus belzutifan resulted in improved disease-free survival compared to pembrolizumab plus placebo.

Sources:

• The New England Journal of Medicine