Until recently, sunitinib was the only adjuvant treatment option for patients with high-risk, resectable renal-cell carcinoma (RCC), but the adverse event profile and conflicting efficacy data have led to limited uptake of adjuvant therapy for RCC in clinical practice. Pembrolizumab is an immune checkpoint inhibitor that has shown efficacy in combination with axitinib and lenvatinib in patients with advanced RCC.1
In the phase 3 KEYNOTE-564 trial, 994 adults with clear-cell RCC at high risk for disease recurrence were enrolled. In this study, high-risk disease was defined as stage T2 with nuclear grade 4 or sarcomatoid differentiation, stage T3 or higher, regional lymph node metastasis, or surgically resectable distant oligometastasis with no evidence of disease. Within 12 weeks of nephrectomy with or without metastasectomy, participants were randomized to receive adjuvant pembrolizumab 200 mg every 3 weeks or placebo for up to 17 cycles. The primary end point was investigator-assessed disease-free survival (DFS), and overall survival (OS) was a key secondary end point.1
At a prespecified interim analysis (median follow-up, 24 months), pembrolizumab was associated with a 32% decreased risk for disease recurrence or death (hazard ratio, 0.68; 95% confidence interval, 0.53-0.87; P = .002). Median DFS was not reached in either arm of the trial. The 2-year DFS rate was 77.3% with pembrolizumab and 68.1% with placebo. Corresponding 1-year DFS rates were 85.7% and 76.2%. Median OS was not reached in either treatment arm. Pembrolizumab was associated with a 46% decreased risk for death relative to placebo (hazard ratio, 0.54; 95% confidence interval, 0.30-0.96). The 2-year OS rate was 96.6% with pembrolizumab and 93.5% with placebo.1
Pembrolizumab was associated with more adverse events of hypothyroidism, hyperthyroidism, pruritus, and rash. Adverse events led to treatment discontinuations in 20.7% of patients in the pembrolizumab group and 2.0% of patients in the placebo group.1
The study investigators concluded that adjuvant pembrolizumab significantly improved DFS in a clinically meaningful manner versus placebo for patients at high risk for disease recurrence.1 The results of the KEYNOTE-564 trial led to the approval of adjuvant pembrolizumab in November 2021.2
- Choueiri TK, Tomczak P, Park SH, et al; for the KEYNOTE-564 Investigators. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385:683-694.
- US Food and Drug Administration. FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. November 17, 2021. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma. Accessed December 9, 2021.