Clinical Report: Can Belzutifan Improve Adjuvant Therapy?

Overview

The combination of pembrolizumab plus belzutifan demonstrated improved disease-free survival compared to pembrolizumab plus placebo in patients with surgically resected clear-cell renal-cell carcinoma at increased risk for recurrence. However, higher rates of grade 3 or higher adverse events were observed with the combination therapy.

Background

Adjuvant therapy for clear-cell renal-cell carcinoma (ccRCC) is critical for patients at increased risk of recurrence following nephrectomy. The standard of care has been established with pembrolizumab based on the KEYNOTE-564 study. The LITESPARK-022 trial investigates the potential benefits of adding belzutifan, a HIF-2α inhibitor, to this regimen.

Data Highlights

Key Findings

• Higher disease-free survival rates were observed with pembrolizumab plus belzutifan compared to pembrolizumab plus placebo.
• Grade 3 or higher adverse events occurred in 52% of patients receiving the combination therapy.
• Anemia was reported in 84% of patients receiving pembrolizumab plus belzutifan.
• Overall survival data remained immature at the first interim analysis, with 96% estimated survival at 24 months for both groups.
• Serious adverse events occurred in 30% of patients receiving pembrolizumab plus belzutifan.

Clinical Implications

Clinicians should be aware of the increased risk of severe adverse events associated with this combination therapy.

Conclusion

Adjuvant pembrolizumab plus belzutifan resulted in higher disease-free survival than pembrolizumab plus placebo among patients with clear-cell renal-cell carcinoma at increased risk for recurrence.

Related Resources & Content

1. Choueiri TK, et al., NEJM, 2026 -- Adjuvant Pembrolizumab Plus Belzutifan for Renal-Cell Carcinoma
2. FDA, 2026 -- FDA approves belzutifan with pembrolizumab for adjuvant treatment of renal cell carcinoma
3. The ASCO Post — Adjuvant Pembrolizumab Plus Belzutifan in Patients With RCC at Increased Risk of Recurrence
4. The ASCO Post — Adjuvant Pembrolizumab Plus Belzutifan in Patients With RCC at Increased Risk of Recurrence
5. The ASCO Post — Adjuvant Pembrolizumab Plus Belzutifan in Patients With RCC at Increased Risk of Recurrence
6. The ASCO Post — Belzutifan in Previously Treated Advanced Renal Cell Carcinoma
7. Adjuvant Pembrolizumab Plus Belzutifan in Patients With RCC at Increased Risk of Recurrence
8. https://acinoedudoc.com/wp-content/uploads/2026/01/2024-Powles-et-al.-Renal-cell-carcinoma-ESMO-Clinical-Practice-Guideline-for-diagnosis-treatment-and-follow-up.pdf
9. Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma | New England Journal of Medicine
10. FDA approves belzutifan with pembrolizumab for adjuvant treatment of renal cell carcinoma | FDA