The double-blind, multicenter, randomized KEYNOTE-564 study (NCT03142334) is the first positive phase 3 study of adjuvant immunotherapy for patients (pts) with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence after nephrectomy or nephrectomy and resection of metastatic lesions. Adjuvant pembrolizumab resulted in a statistically significant improvement in disease-free survival (DFS) vs placebo with 24 months of follow-up (HR 0.68, 95% CI 0.53−0.87; P = 0.0010 [one-sided]). We present updated efficacy and safety results from KEYNOTE-564 with 6 months of additional follow-up.
Pts had histologically confirmed, clear cell RCC (pT2, grade 4 or sarcomatoid, N0 M0; pT3 or pT4, any grade, N0 M0; any pT, any grade, N+ M0; or M1 NED [no evidence of disease after primary tumor and soft tissue metastases completely resected ≤1 year from nephrectomy]) and had undergone surgery ≤12 weeks prior to randomization. The primary endpoint was DFS by investigator assessment in all randomized pts (ITT population). Overall survival (OS) was a key secondary endpoint. Safety/tolerability in all treated pts was a secondary endpoint.
994 pts were randomized 1:1 to pembrolizumab (N = 496) or placebo (N = 498). As of data cutoff date of June 14, 2021, median (range) follow-up, defined as time from randomization to data cutoff, was 30.1 (20.8−47.5) months. In this updated analysis, DFS benefit with pembrolizumab was maintained (HR 0.63, 95% CI 0.50−0.80; nominal P < 0.0001) and was consistent across subgroups, including pts with M0 disease with intermediate-high risk of recurrence (HR 0.68, 95% CI 0.52−0.89), M0 high risk of recurrence (HR 0.60, 95% CI 0.33−1.10), or M1 NED (HR 0.28, 95% CI 0.12−0.66). The estimated DFS rate at 24 months was 78.3% with pembrolizumab vs 67.3% with placebo. A total of 66 OS events were observed, 23 in the pembrolizumab arm and 43 in the placebo arm (HR 0.52, 95% CI 0.31−0.86; P = 0.0048); the p-value did not cross the statistical hypothesis testing boundary and additional follow-up is planned for this key secondary endpoint. The estimated OS rate at 24 months was 96.2% with pembrolizumab vs 93.8% with placebo. With additional follow-up, no increase in any-grade or grade 3-4 adverse events, or steroid use for immune-mediated adverse events was observed. No deaths related to pembrolizumab occurred.
At 30 months of follow-up, adjuvant pembrolizumab continued to demonstrate a consistent and clinically meaningful improvement in DFS vs placebo in pts with RCC at high risk of recurrence. No new safety signals were observed with pembrolizumab in the adjuvant setting. Clinical trial information: NCT03142334.