Adjuvant pembrolizumab could be a new standard of care for patients with clear cell renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy, according to researchers.1 

Updated results from the KEYNOTE-564 trial showed that adjuvant pembrolizumab can improve disease-free survival (DFS), when compared with placebo, in this patient group. These results were published in The Lancet Oncology.

KEYNOTE-564 ( Identifier: NCT03142334) is a double-blind, phase 3 trial that included 994 patients who had clear cell RCC and an increased risk of recurrence after nephrectomy. The patients were randomly assigned to receive adjuvant pembrolizumab at 200 mg (n=496) or placebo (n=498) every 3 weeks for up to 17 cycles. 

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Results of the first interim analysis showed a significant improvement in DFS with pembrolizumab at a median follow-up of 24.1 months (hazard ratio [HR], 0.68; 95% CI, 0.53-0.87; P =.002).2

With an additional 6 months of follow-up (median, 30.1 months), DFS remained significantly improved for patients assigned to pembrolizumab (HR, 0.63; 95% CI, 0.50-0.80).1 

The median DFS was not reached in either treatment arm. The 30-month DFS rate was 75.2% in the pembrolizumab arm and 65.5% in the placebo arm. 

Subsequent therapy was given to 14% of patients assigned to pembrolizumab and 20% of patients assigned to placebo. 

The median time to first subsequent therapy or death from any cause was not reached in either treatment arm. However, the risk was lower in the pembrolizumab arm (HR, 0.67; 95% CI, 0.50-0.90). 

The overall survival data are not yet mature. 

The most common grade 3-4 adverse events (AEs) in the pembrolizumab arm were hypertension (3%) and increased alanine aminotransferase (2%). In the placebo arm, the most common grade 3-4 AE was hypertension (3%). 

Immune-mediated AEs occurred in 36% of patients in the pembrolizumab arm and 7% of patients in the placebo arm. Serious AEs related to study treatment occurred in 12% and less than 1% of patients, respectively. There were no treatment-related deaths in either arm.

“Additional follow-up and analyses reaffirmed the significant disease-free survival benefit observed in our previous analysis and supported adjuvant pembrolizumab as a potential new standard of care for patients with renal cell carcinoma with an increased risk of disease recurrence after surgery,” the researchers concluded.

Disclosures: This research was supported by Merck Sharp & Dohme LLC. The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. Powles T, Tomczak P, Park SH, et al. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. Published online September 1, 2022. doi: 10.1016/S1470-2045(22)00487-9
  2. Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. N Engl J Med. 2021;385: 683-94.

This article originally appeared on Cancer Therapy Advisor