On November 17, 2021, the FDA accelerated the approval of a new indication for pembrolizumab (Keytruda; Merck), for the adjuvant treatment of patients with renal-cell carcinoma (RCC) at intermediate-high or high risk for recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.
This approval was evaluated in the KEYNOTE-564 study, a multicenter, randomized, double-blind, placebo-controlled clinical trial of 994 patients with RCC at intermediate-high or high risk for recurrence, or for patients with no evidence of disease. The patients were randomized in a 1:1 ratio to pembrolizumab every 3 weeks or to placebo for up to 1 year, until disease recurrence or unacceptable adverse events.
The primary end point was investigator-assessed disease-free survival (DFS), defined as time to recurrence, metastasis, or death. The overall survival (OS) was a secondary end point. At a prespecified interim analysis, significant improvement in DFS was demonstrated, including 109 (22%) DFS events in the pembrolizumab arm and 151 (30%) DFS events in patients receiving placebo (hazard ratio, 0.68; 95% confidence interval, 0.53-0.87; P = .0010). The median DFS was not reached in either arm. At the time of the analysis, OS data were not mature, and 5% of deaths were reported in the overall population.
The most common (≥20%) adverse reactions to pembrolizumab in this study were musculoskeletal pain, fatigue, rash, diarrhea, pruritus, and hypothyroidism.