Adjuvant pembrolizumab improves disease-free and overall survival among patients with resected clear-cell renal-cell carcinoma. The hypoxia-inducible factor 2α inhibitor belzutifan has activity in advanced disease. Adjuvant pembrolizumab with belzutifan may further improve outcomes in patients with clear-cell renal-cell carcinoma increased risk for recurrence.
In this phase 3, double-blind trial, we randomly assigned participants in a 1:1 ratio to receive intravenous pembrolizumab a dose of 400 mg every 6 weeks (≤9 doses) and either daily oral belzutifan a dose of 120 mg (pembrolizumab–belzutifan) or placebo (pembrolizumab–placebo) for up to 1 year. The primary end point was disease-free survival as assessed by the investigator; secondary end points included overall survival and safety. Research Summary Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma
A total of 921 participants were assigned to receive pembrolizumab–belzutifan and 920 were assigned to receive pembrolizumab–placebo. The median time from randomization to the data-cutoff date (August 23, 2025) was 28.4 months (range, 15.0 to 40.1). Disease-free survival was significantly higher with pembrolizumab–belzutifan than with pembrolizumab–placebo (hazard ratio for disease recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87; two-sided P
Treatment with pembrolizumab–belzutifan led to significantly higher disease-free survival, with a greater risk of grade 3 or higher toxic effects, than treatment with pembrolizumab monotherapy after nephrectomy in participants with clear-cell renal-cell carcinoma increased risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; LITESPARK-022 ClinicalTrials.gov number, NCT05239728.)
Belzutifan beat everolimus in progression-free survival (PFS) and response rate, but hardly anyone uses it alone, mostly used in combination with Lenvatinib.
It is yet another option for renal cell cancer patients.
This is helpful when we get patients who have a renal mass as this may help distinguish between benign vs malignant.
Adjuvant pembrolizumab improves overall survival (reduced mortality by 38%). We need to make sure that urologists are also aware so those patients with a high risk of recurrence can get this medication.
An intriguing study from the UK, patients had 24 weeks of sunitinib or pazopanib followed by a continuation or treatment holiday. Non-inferiority could not be established, but there was seemingly no meaningful reduction in OS (28 vs. 27 months overall), with a noticeable improvement in toxicity in the treatment break group. This may be a realistic strategy for patients with a focus on QOL or cost-effectiveness.
Pembrolizumab remains the only adjuvant option for high risk RCC after curative surgery. The OS curves seem to be beginning to separate and hope to be positive with longer f/u. The ongoing Durvalumab + Tremilumumab will be an interesting adjuvant study for RCC when the results are available.