The phase 3 KEYNOTE-564 trial (NCT03142334) enrolled patients with intermediate-high- or high-risk RCC, a group in whom until recently no standard-of-care existed after surgery, explained Prof. Thomas Powles (University College London, UK). Participants were randomised to adjuvant pembrolizumab (n=496) or placebo (n=498). The primary analysis, published in the New England Journal of Medicine, displayed a significant disease-free survival (DFS) benefit for patients who were treated with pembrolizumab over those who received placebo . Prof. Powles presented the updated results of this trial after a median follow-up of 30.1 months.
After 30.1 months of follow-up, the DFS was still significantly higher in the pembrolizumab arm than in the placebo arm (HR 0.63; P<0.0001), with corresponding 24-month DFS rates of 78.3% and 67.3%. This result was consistent across subgroups, including disease risk category and PD-L1 status. Importantly, an exploratory analysis indicated that the rate of distant recurrences was higher in the placebo arm than in the pembrolizumab arm (HR 0.63), both in patients with M0-disease (n=936; 29.0% vs 20.8%) and in patients with M1-disease (n=58; 55.2% vs 20.7%). Prof. Powles added that the overall survival results were not yet mature, with 66 out of 200 needed events, but that a promising trend could be observed (HR 0.52; 95% CI 0.31–0.86).
The updated safety analysis did not reveal a substantial increase in adverse events (AEs). Fatigue (20.3%), pruritis (18.6%), hypothyroidism (17.4%), diarrhoea (15.8%), and rash (15.0%) were the most common any-grade AEs in the pembrolizumab arm.
1. Powles T, et al. Pembrolizumab (pembro) as adjuvant therapy for patients (pts) with renal cell carcinoma (RCC): Updated results from the 30-month follow-up of KEYNOTE-564. Game-changing session 2, EAU 2022, 01–04 July.
2. Chouieri TK, et al. N Engl J Med 2021;385:683–694.