ASCO GU 2022: KEYNOTE-564 Update Confirms Benefits of Adjuvant Pembrolizumab in Renal Cell Carcinoma
Follow-up is ongoing, as overall survival data remain immature
February 19, 2022— San Francisco, California—An update of the KEYNOTE-564 trial confirms the benefit of adjuvant pembrolizumab for patients with renal cell carcinoma who have risk features for recurrence, according to research presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium, which took place here and online from February 17 to 19.
“Kidney cancer, globally, is a killer and was responsible for nearly 180,000 deaths worldwide in 2020,” said lead author Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute at Brigham and Women’s Hospital in Boston, during his presentation of the data. “Nephrectomy remains the standard-of-care therapy for locoregional renal cell cancer. We conducted KEYNOTE-564, a phase III, double-blind, multicenter trial of pembrolizumab versus placebo after surgery in participants with renal cell cancer. At the last ASCO meeting, we reported its primary endpoint for the protocol-specified outcome at the first interim analysis. Adjuvant pembrolizumab resulted in a statistically significant and clinically meaningful disease-free survival (DFS) benefit versus placebo, with a 32% decrease in the risk of recurrence and death. Since that time, adjuvant pembrolizumab was approved in the United States, European Union, and Brazil [for select patients with renal cell carcinoma].”
For KEYNOTE-564, 994 patients with histologically confirmed renal cell carcinoma who were M0 intermediate-high, M0 high risk, or M1 with no evidence of disease after surgery were randomized to pembrolizumab 200 mg every 3 weeks (n = 496) or placebo (n = 498) for about 1 year. The median time from randomization to cut-off was 30.1 months. At ASCO GU 2022, Dr. Choueiri reported on the results an additional 6 months after the initial interim results at 24 months.
Patients’ median age was about 60 years, about 70% were male, and nearly three-quarters had an ECOG performance status of 1. The majority (86%) were intermediate-high risk, and about 75% had a PD-L1 combined positive score ≥ 1.
In this updated analysis, DFS benefit with pembrolizumab was maintained, with a hazard ratio of 0.63 (95% confidence interval 0.50–0.80, nominal P <.0001), This was consistent across subgroups, including among patients with M0 disease who were at intermediate-high risk of recurrence (hazard ratio 0.68, 95% confidence interval 0.52–0.89), M0 at high risk of recurrence (hazard ratio 0.60, 95% confidence interval 0.33–1.10), or M1 with no evidence of disease (hazard ratio 0.28, 95% confidence interval 0.12–0.66).
A total of 66 overall survival (OS) events were observed, 23 in the pembrolizumab arm and 43 in the placebo arm, for an OS hazard ratio of 0.52 (95% confidence interval 0.31–0.86, P = .0048). The P value did not cross the statistical hypothesis testing boundary, and additional follow-up is planned for this key secondary endpoint. The estimated OS rate at 24 months was 96.2% with pembrolizumab versus 93.8% with placebo.
There was no increase in any grade or grade 3 to 4 adverse events with the additional 6 months of follow-up, nor was there any steroid use for immune-mediated adverse events. No deaths related to pembrolizumab occurred.
“Adjuvant pembrolizumab continued to demonstrate a DFS benefit versus placebo in participants with renal cell cancer with intermediate-high or high risk of recurrence or M1 no evidence of disease after surgery, with no new safety signals,” concluded Dr. Choueiri. “This updated analysis of the KEYNOTE-564 study further supports adjuvant pembrolizumab as a new standard of care for patients with renal cell carcinoma with risk features of recurrence.” Follow-up is ongoing for this trial.
The KEYNOTE-564 trial was sponsored and conducted in collaboration with Merck Sharp & Dohme Corp.
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