KEYNOTE-564
Adjuvant pembrolizumab versus placebo after nephrectomy in clear-cell renal-cell carcinoma at high risk of recurrence (KEYNOTE-564)
Phase 3N = 994NCT03142334
- Population
- Clear-cell renal-cell carcinoma at high risk of recurrence after nephrectomy, with or without metastasectomy.
- Design
- Double-blind phase 3 trial, randomised 1:1. Pembrolizumab 200 mg or placebo intravenously once every 3 weeks for up to 17 cycles (about 1 year). Primary endpoint investigator-assessed disease-free survival; overall survival was a key secondary endpoint. The ClinicalTrials.gov record lists actual enrolment of 994, the sum of the two arms in the abstract.
- Primary endpoint
- DFS
- Arms
- Pembrolizumab (experimental, n = 496): Pembrolizumab 200 mg intravenously every 3 weeks for up to 17 cycles
- Placebo (control, n = 498): Placebo intravenously every 3 weeks for up to 17 cycles
- People
- Choueiri TK
DFSHR 0.68 (95% CI 0.53–0.87)Δ 24-month DFS+9.2 pointsOSHR 0.54 (95% CI 0.30–0.96)Δ 24-month OS+3.1 pointsDFSHR 0.72 (95% CI 0.59–0.87)OSHR 0.62 (95% CI 0.44–0.87)
Show the numbers
| Endpoint | Analysis | Pembrolizumab | Placebo | Effect |
|---|---|---|---|---|
| DFSRandomised patients (analysis population not stated in the abstract)Disease-free survival according to the investigator's assessment. | interimmedian follow-up 24.1 monthsChoueiri 2021 | 77.3% at 2 y | 68.1% at 2 y | HR 0.68 (95% CI 0.53–0.87)P=0.002Median time from randomisation to the data cutoff at the prespecified interim analysis; two-sided P. Grade 3 or higher adverse events of any cause occurred in 32.4% with pembrolizumab and 17.7% with placebo; no deaths were related to pembrolizumab. |
| OSRandomised patients (analysis population not stated in the abstract) | interimmedian follow-up 24.1 monthsChoueiri 2021 | 96.6% at 2 y | 93.5% at 2 y | HR 0.54 (95% CI 0.30–0.96)Estimated percentage alive at 24 months at the prespecified interim analysis; overall survival was a key secondary endpoint. |
| DFSRandomised participants (analysis population not stated in the abstract)Disease-free survival according to the investigator's assessment. | interimmedian follow-up 57.2 monthsChoueiri 2024 | — | — | HR 0.72 (95% CI 0.59–0.87)Described as consistent with previous analyses; reported with the third prespecified interim analysis of overall survival. |
| OSRandomised participants (analysis population not stated in the abstract) | interimmedian follow-up 57.2 monthsChoueiri 2024 | 91.2% at 4 y | 86% at 4 y | HR 0.62 (95% CI 0.44–0.87)P=0.005Third prespecified interim analysis; overall survival was the key secondary endpoint. Serious adverse events of any cause occurred in 20.7% with pembrolizumab and 11.5% with placebo, and grade 3 or 4 adverse events related to pembrolizumab or placebo in 18.6% and 1.2%; no deaths were attributed to pembrolizumab. |
| Endpoint | Analysis | Pembrolizumab | Placebo | Effect |
|---|---|---|---|---|
| DFSRandomised patients (analysis population not stated in the abstract)Disease-free survival according to the investigator's assessment. | interimmedian follow-up 24.1 monthsChoueiri 2021 | 77.3% at 2 y | 68.1% at 2 y | HR 0.68 (95% CI 0.53–0.87)P=0.002Median time from randomisation to the data cutoff at the prespecified interim analysis; two-sided P. Grade 3 or higher adverse events of any cause occurred in 32.4% with pembrolizumab and 17.7% with placebo; no deaths were related to pembrolizumab. |
| OSRandomised patients (analysis population not stated in the abstract) | interimmedian follow-up 24.1 monthsChoueiri 2021 | 96.6% at 2 y | 93.5% at 2 y | HR 0.54 (95% CI 0.30–0.96)Estimated percentage alive at 24 months at the prespecified interim analysis; overall survival was a key secondary endpoint. |
| DFSRandomised participants (analysis population not stated in the abstract)Disease-free survival according to the investigator's assessment. | interimmedian follow-up 57.2 monthsChoueiri 2024 | — | — | HR 0.72 (95% CI 0.59–0.87)Described as consistent with previous analyses; reported with the third prespecified interim analysis of overall survival. |
| OSRandomised participants (analysis population not stated in the abstract) | interimmedian follow-up 57.2 monthsChoueiri 2024 | 91.2% at 4 y | 86% at 4 y | HR 0.62 (95% CI 0.44–0.87)P=0.005Third prespecified interim analysis; overall survival was the key secondary endpoint. Serious adverse events of any cause occurred in 20.7% with pembrolizumab and 11.5% with placebo, and grade 3 or 4 adverse events related to pembrolizumab or placebo in 18.6% and 1.2%; no deaths were attributed to pembrolizumab. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 0.68 | 0.53–0.87 |
| OS | 0.54 | 0.3–0.96 |
| DFS | 0.72 | 0.59–0.87 |
| OS | 0.62 | 0.44–0.87 |
Appears in
Sources
Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, et al. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med. 2021;385(8):683-694.
Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Symeonides SN, et al. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024;390(15):1359-1371.