Choueiri, Toni K.
Adjuvant pembrolizumab plus belzutifan for renal-cell carcinoma - páginas: 32-43
Background:
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 at increased risk for recurrence.
Methods:
In this phase 3, double-blind trial, we randomly assigned participants in a 1:1 ratio to receive intravenous pembrolizumab at a dose of 400 mg every 6 weeks (≤9 doses) and either daily oral belzutifan at 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.
Results:
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<0.001); the estimated 24-month disease-free survival was 80.7% and 73.7%, respectively. At this interim analysis with 29% of the final-analysis events observed, overall survival did not differ significantly between the groups (hazard ratio for death, 0.78; 95% CI, 0.51 to 1.19; two-sided P=0.24); the estimated 24-month overall survival was 96.2% with pembrolizumab–belzutifan and 95.7% with pembrolizumab–placebo. Adverse events of grade 3 or higher occurred in 52.1% of the participants who received pembrolizumab–belzutifan and in 30.2% of those who received pembrolizumab–placebo.
Conclusions:
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 at increased risk for recurrence.
CÁNCER GENITOURINARIO
NEFROLOGÍA GENERAL
TRATAMIENTOS DE ONCOLOGÍA
Adjuvant pembrolizumab plus belzutifan for renal-cell carcinoma - páginas: 32-43
Background:
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 at increased risk for recurrence.
Methods:
In this phase 3, double-blind trial, we randomly assigned participants in a 1:1 ratio to receive intravenous pembrolizumab at a dose of 400 mg every 6 weeks (≤9 doses) and either daily oral belzutifan at 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.
Results:
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<0.001); the estimated 24-month disease-free survival was 80.7% and 73.7%, respectively. At this interim analysis with 29% of the final-analysis events observed, overall survival did not differ significantly between the groups (hazard ratio for death, 0.78; 95% CI, 0.51 to 1.19; two-sided P=0.24); the estimated 24-month overall survival was 96.2% with pembrolizumab–belzutifan and 95.7% with pembrolizumab–placebo. Adverse events of grade 3 or higher occurred in 52.1% of the participants who received pembrolizumab–belzutifan and in 30.2% of those who received pembrolizumab–placebo.
Conclusions:
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 at increased risk for recurrence.
CÁNCER GENITOURINARIO
NEFROLOGÍA GENERAL
TRATAMIENTOS DE ONCOLOGÍA