Adjuvant Pembrolizumab Significantly Improved Overall Survival Among Patients With Clear-Cell Renal Cell Carcinoma at Increased Risk of Recurrence

According to interim analysis results from the phase 3 KEYNOTE-564 trial, adjuvant pembrolizumab significantly improved overall survival (OS) compared to placebo among patients with clear-cell renal cell carcinoma at increased risk of recurrence after surgical resection. 

“Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial,” wrote Toni Choueiri, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors. “Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.” 

This double-blind, placebo-controlled trial enrolled 994 patients who underwent surgical resection for clear-cell renal cell carcinoma at increased risk of disease recurrence. Patients were randomized on a 1-to-1 basis to receive either 200 mg of pembrolizumab (n = 496) or placebo (n = 498) every 3 weeks for up to 17 cycles or until disease recurrence, unacceptable toxicity, or consent withdrawal. Primary end points included OS and safety. 

Estimated 48-month OS was 91.2% in the pembrolizumab arm and 86% in the placebo arm (hazard ratio, 0.62; 95% confidence interval, 0.44 to 0.87; P = .005). Serious adverse events of any cause occurred in 20.7% of patients in the pembrolizumab arm and 11.5% of patients in the placebo arm. Grade 3/4 treatment-related adverse events occurred in 18.6% of patients in the pembrolizumab arm and 1.2% of patients in the placebo arm.

Dr Choueiri et al, concluded, “Adjuvant pembrolizumab was associated with a significant and clinically meaningful improvement in overall survival, as compared with placebo, among participants with clear-cell renal-cell carcinoma at increased risk for recurrence after surgery.” 

Source: 

Choueiri TK, Tomczak P, Park SH, et al. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. Published online: April 17, 2024. doi: 10.1056/NEJMoa2312695