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.
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