Multinational phase 3 trial of adjuvant pembrolizumab for clear cell renal cell carcinoma: five-year results from KEYNOTE-564

The multinational phase 3 KEYNOTE-564 trial established adjuvant pembrolizumab as the standard of care for clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence. The fourth prespecified interim analysis of the trial, with a minimum follow-up of five years, has now been published. Patients were randomized 1:1 to adjuvant pembrolizumab 200 mg (n=496) or placebo (n=498) every 3 weeks following nephrectomy of nephrectomy and metastasectomy. Treatment continued for up to 17 cycles, until recurrence, or until treatment discontinuation criteria were met. The primary endpoint was disease-free survival (DFS) assessed by local investigators. Median follow-up duration was 70 months (range 60-87). Median DFS was not reached in the pembrolizumab group and was 68 months in the placebo group (HR 0.71; 95% CI 0.59-0.86), with estimated 5-year DFS rates 60.9% versus 52.2%; median overall survival (OS) was not reached in both arms (0.66; 0.48-0.90), with estimated 5-year OS rates of 87.7% versus 82.3%. DFS and OS beneftis were consistent across key subgroups. Safety was largely unchanged since the previous analysis. The authors conclude that after a median follow-up of 70 months, adjuvant pembrolizumab demonstrated sustained DFS and OS benefit among patients with ccRCC at increased risk of recurrence.