Adjuvant pembrolizumab improves survival in patients with clear-cell renal cell carcinoma

April 2024 Cancer trials Andrea Enguita
Human kidney cross section on scientific background. 3d illustration

Previously, the KEYNOTE-564 trial demonstrated improved disease-free survival with adjuvant pembrolizumab in patients with clear-cell renal cell carcinoma (RCC). A recent interim analysis published in The New England Journal of Medicine now reveals that this improvement in disease-free survival translates into an overall survival benefit for these patients.

Pembrolizumab, an anti-programmed death 1 (PD-1) antibody, was approved in 2021 as adjuvant treatment for patients with renal cell carcinoma (RCC) with intermediate-to-high or high risk of recurrence after nephrectomy, with or without the resection of metastatic lesions. This approval was based on the significant and clinically meaningful improvement in disease-free survival observed with pembrolizumab in the phase III KEYNOTE-564 trial. A recent interim analysis from the same trial now presents results regarding overall survival (OS).


The phase III KEYNOTE-564 trial enrolled patients with clear-cell (cc) RCC who had an increased risk of recurrence after surgery. In total, 994 participants were randomly assigned (1:1) to receive pembrolizumab at a dose of 200 mg (n=496) or placebo (n=498) every three weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent. Disease-free survival was the primary endpoint, while overall survival (OS) was the key secondary endpoint.


After a median follow-up of 57.2 months, the disease-free survival benefit was consistent with previous analyses and in favour of adjuvant pembrolizumab (HR[95%CI]: 0.72[0.59-0.87]). A significant improvement in OS was observed with pembrolizumab compared to placebo (HR[95%CI]: 0.62[0.44-0.87]; p=0.005). At 48 months, OS rates stood at 91.2% vs. 86.0% in the pembrolizumab and placebo groups, respectively. This benefit was consistent across key subgroups. Pembrolizumab was associated with a higher incidence of serious adverse events (AEs) of any cause (20.7% vs. 11.5% with placebo) and of grade 3-4 AEs related to pembrolizumab or placebo (18.6% vs. 1.2%). No deaths were attributed to pembrolizumab therapy.


Adjuvant pembrolizumab was associated with a significant and clinically meaningful improvement in OS compared with placebo in patients with ccRCC at increased risk for recurrence after surgery.


Choueiri T, Tomczak P, Park SH, et al. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024;390:1359-71.