Adjuvant pembrolizumab for the treatment of clear cell renal cell carcinoma: Five-year results from the phase III KEYNOTE-564 study
In brief
Adjuvant pembrolizumab lifts 5-year disease-free survival to 61% versus 52% with placebo
In the phase III KEYNOTE-564 trial, patients with high-risk clear cell kidney cancer who received one year of pembrolizumab after surgery had an estimated 5-year disease-free survival of 60.9% compared with 52.2% for placebo, and a 5-year overall survival of 87.7% versus 82.3%. Benefits were consistent across subgroups and safety remained unchanged, reinforcing pembrolizumab as the adjuvant standard.
- Journal
- Annals of oncology : official journal of the European Society for Medical Oncology (Q1)
- Published
- 26 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- N B Haas, T B Powles, P Tomczak, S H Park, B Venugopal, S N Symeonides, et al.
- PMID
- 42648402
- DOI
- 10.1016/j.annonc.2026.08.006
Why clinicians should know about it
- Picked for Breast and Endocrine Surgery (top studies of the week, 30 August 2026): High-quality evidence in a top journal
- Picked for Oncology and Radiation Oncology (top studies of the week, 30 August 2026): Phase III adjuvant pembrolizumab trial with DFS/OS
- Picked for Surgery (top studies of the week, 30 August 2026): High-quality evidence in a top journal
Abstract
BACKGROUND: The randomized phase III study KEYNOTE-564 (NCT03142334) established pembrolizumab after surgery as the standard of care for patients with clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence. Prior analyses showed significantly improved disease-free survival (DFS) and overall survival (OS) with adjuvant pembrolizumab versus placebo. We present results from the fourth prespecified interim analysis, with a minimum follow-up of five years. PATIENTS AND METHODS: Eligible adults with ccRCC at increased risk of recurrence were randomly assigned 1:1 to adjuvant pembrolizumab 200 mg or placebo every 3 weeks following nephrectomy or following nephrectomy and metastasectomy. Study treatment continued for ≤17 cycles (∼1 year), until recurrence, or until treatment discontinuation criteria were met. The primary endpoint was DFS per investigator assessment, and the key secondary endpoint was OS. Safety was a secondary endpoint. RESULTS: Overall, 994 participants were randomized to pembrolizumab (n = 496) or placebo (n = 498). Median time from randomization to data cutoff (September 25, 2024) was 70 months (range, 60-87). Pembrolizumab improved DFS versus placebo (hazard ratio [HR] 0.71, 95% CI 0.59-0.86); median DFS was not reached (NR) versus 68 months, and estimated 5-year DFS rates were 60.9% versus 52.2%, respectively. OS was improved with pembrolizumab over placebo (HR 0.66, 95% CI 0.48-0.90); median OS was NR for both arms with an estimated 5-year OS rate of 87.7% and 82.3%, respectively. DFS and OS benefits were consistent across key subgroups. Safety was largely unchanged since last analysis. CONCLUSIONS: After a median follow-up of 70 months, adjuvant pembrolizumab demonstrated sustained DFS and OS benefit and a safety profile consistent with prior analyses. These findings continue to support the use of adjuvant pembrolizumab in ccRCC at increased risk of recurrence.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.