Updated data from the KEYNOTE-564 trial shows pembrolizumab disease-free survival persists long term versus placebo as neoadjuvant therapy for renal cell carcinoma (RCC). With 33% of events needed, overall survival data are not yet mature; however, the hazard ratio is declining.


While nephrectomy is the standard of care treatment for locoregional RCC, nearly one-half of patients eventually experience disease recurrence after surgery, which is associated with shortened life expectancy. Effective perioperative therapy to reduce this risk remains an unmet need. The phase III, randomized KEYNOTE-564 trial (NCT03142334) evaluated the effect of pembrolizumab versus placebo as adjuvant therapy for patients with RCC. A total of 994 patients with histologically confirmed clear-cell RCC were enrolled in the study and randomized 1:1 to pembrolizumab or placebo.

Primary Endpoint Met

The primary endpoint was DFS in all randomized patients. Overall survival (OS) was a key secondary endpoint, as were safety and tolerability. The study met its primary endpoint at the first interim analysis.1 Adjuvant pembrolizumab resulted in a statistically significant improvement in disease-free survival (DFS) versus placebo with 24 months of follow-up (HR 0.68, P=0.0010). Dr. Toni Choueiri (Dana-Farber Cancer Institute) presented updated efficacy and safety results from KEYNOTE-564 with 6 months of additional follow-up.2

DFS benefit with pembrolizumab was maintained (HR 0.63; P<0.0001) and was consistent across subgroups (M0 intermediate-high risk (n=855): HR 0.68; M0 high-risk (n=76): HR 0.60; and M1 NED (n=58): HR 0.28). The estimated DFS rate at 24 months was 78.3% with pembrolizumab versus 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; P = 0.0048; the P-value did not cross the statistical hypothesis testing boundary for this endpoint).

Declining Overall Survival HR

However, compared with results from the first interim analysis, the hazard ratio for OS is declining and significancy is increasing (HR 0.54; P=0.0164 at 24 months follow-up vs HR 0.52; P=0.0048 at 30 months follow-up). 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. “Adjuvant pembrolizumab continues to demonstrate a DFS benefit versus placebo in patients with RCC, with no new safety signals,” concluded Dr. Choueiri. “Additional follow-up is planned for OS analysis. This updated analysis supports adjuvant pembrolizumab as a new standard of care for patients with RCC with risk features for recurrence.”

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