The Food and Drug Administration (FDA) has approved Keytruda® (pembrolizumab) as adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. 

The approval was based on data from the pivotal phase 3 KEYNOTE-564 trial ( Identifier: NCT03142334), which compared the efficacy and safety of pembrolizumab monotherapy to placebo for the adjuvant treatment of 994 adults with RCC who have undergone nephrectomy and who have intermediate-high, high risk, or M1 no evidence of disease (M1 NED) RCC with clear cell component. Patients were randomly assigned 1:1 to receive either pembrolizumab 200mg intravenously (IV) on day 1 of each 3-week cycle for up to 17 cycles or placebo. The primary endpoint was disease-free survival (DFS); key secondary endpoints included overall survival (OS) and safety.

Results showed that pembrolizumab met the primary endpoint reducing the risk of disease recurrence or death by 32% at a median follow-up of 24 months vs placebo (hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P =.001); the median DFS was not reached in either treatment arm. At 24 months, the estimated DFS rate was 77.3% with pembrolizumab vs 68.1% with placebo. Though not reached at the time of analysis, a favorable trend in OS was observed with a 46% reduction in the risk of death with pembrolizumab vs placebo (HR, 0.54; 95% CI, 0.30-0.96; P = .0164). 

As for safety, the most common adverse reactions (all grades greater than or equal to 20%) for pembrolizumab were musculoskeletal pain, fatigue, rash, diarrhea, pruritus, and hypothyroidism.

“In KEYNOTE-564, pembrolizumab reduced the risk of disease recurrence or death by 32%, providing a promising new treatment option for certain patients at intermediate-high or high risk of recurrence,” said Dr. Toni K. Choueiri, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and professor of medicine, Harvard Medical School. “With this FDA approval, pembrolizumab may address a critical unmet treatment need and has the potential to become a new standard of care in the adjuvant setting for appropriately selected patients.”


FDA approves Merck’s Keytruda® (pembrolizumab) as adjuvant therapy for certain patients with renal cell carcinoma (RCC) following surgery. News release. Merck. Accessed November 18, 2021.