03158nam a2200289   4500001000800000005001700008007000300025008004100028040000800069041000800077100003700085245006800122300002100190520223500211650003502446650003202481650003902513700003002552700002702582700002402609700003002633700002302663700002402686773011002710942003102820999001702851ESSALUD20260804122828.0ta      t        pe ||||| |||| 00| 0 spa d  aBMG  aeng  aChoueiri, Toni K. eAutor953653  aAdjuvant pembrolizumab plus belzutifan for renal-cell carcinoma  apáginas: 32-43  aBackground: 
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.  aCÁNCER GENITOURINARIO953654  aNEFROLOGÍA GENERAL953655  aTRATAMIENTOS DE ONCOLOGÍA953656  aMotzer, Robert J. 953657  aKaram, Jose A. 953658  aYip, Wesley 953659  aSuárez, Cristina953660  aYe, Dingwei953661  aHe, Zhisong 9536620 022717922634dMassachusetts NEJM GroupoNEJM001tThe New England Journal of Medicine wESSALUDx0028-4793  cARTICULOSe2026-07-31zsqb  c22723d22723