Adjuvant pembrolizumab (Keytruda) continued to provide a disease-free survival (DFS) benefit in patients with renal-cell carcinoma (RCC) at intermediate-high or high risk of recurrence after nephrectomy, according to 30-month follow-up data from the KEYNOTE-564 trial presented at the 2022 ASCO Genitourinary Cancers Symposium. Previously, at 24 months of follow-up, treatment with pembrolizumab had shown a clinically meaningful improvement in DFS versus placebo in the intent-to-treat population (hazard ratio, 0.68; 95% confidence interval, 0.53-0.87; P = .001) in the trial.
“KEYNOTE-564 was the first positive adjuvant trial to show immunotherapy works in high-risk RCC [after nephrectomy or nephrectomy and resection of metastatic lesions], and primary results were formally presented at the plenary session of ASCO 2021,” said Toni K. Choueiri, MD, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA, and Jerome and Nancy Kohlberg Chair and Professor, Medicine, Harvard Medical School, Boston, who provided attendees with an update on the trial. “At the 2022 Genitourinary Cancers Symposium, we presented 30-month follow-up, updated from the previously reported 24 months. What we saw is that after 6 additional months of follow-up, the hazard ratio went from 0.68 to 0.63, so we had more events for DFS. That was the primary end point, and it remained highly statistically significant.”
“We did an update on adverse events to see if there were any new signals with additional follow-up and there were not. We conclude that this updated analysis of KEYNOTE-564 further supports adjuvant pembrolizumab as a new standard of care in patients with RCC with risk features for recurrence,” he added.
The phase 3, double-blind, multicenter KEYNOTE-564 trial enrolled 994 patients with histologically confirmed clear-cell RCC that was intermediate-high risk (pT2, grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0); high-risk (pT4, any grade, N0, M0; any pT, any grade, N+, M0); or M1 with no evidence of disease after surgery. All patients were randomized in a 1:1 ratio to receive pembrolizumab at 200 mg every 3 weeks (N = 496) or placebo every 3 weeks (N = 498).
Baseline characteristics were well-balanced in the 2 treatment arms. Median patient age was 60 years, and approximately 71% were male. Regarding risk category, 86% in both groups were intermediate-high risk; 40 (8.1%) patients were high risk in the pembrolizumab arm and 7.2% in the placebo arm; and 5.8% of patients in both groups were M1 no evidence of disease. Approximately 11% of both treatment arms had tumors with sarcomatoid features.
The previous analysis at 24 months of follow-up had an estimated DFS rate of 78.3% with pembrolizumab versus 67.3% with placebo. The estimated overall survival rate at 24 months was 96.2% with pembrolizumab versus 93.8% with placebo.
In the updated analysis with 30 months of follow-up, the benefit of adjuvant pembrolizumab was maintained for DFS, with a 37% improvement versus placebo. In intermediate-risk patients, pembrolizumab achieved a 32% improvement in DFS, a 40% improvement in high-risk patients, and a 72% improvement in the M1 no evidence of disease subgroup.
Dr Choueiri noted that longer follow-up is needed to determine whether there will be any improvement in overall survival in the patients who received adjuvant pembrolizumab.
In the updated safety analysis, the percentages of patients in the pembrolizumab arm and placebo arm having an all-cause adverse event were unchanged. Grade 3/4 adverse events were similar at both timepoints for both arms.
“The safety was virtually identical at 24 months and 30 months,” he said.
Invited discussant Daniel Geynisman, MD, Associate Professor, Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, found the longer-term follow-up of the efficacy and safety of KEYNOTE-564 “reassuring.”
“Although we don’t know yet if this [adjuvant pembrolizumab] will result in cure, it definitely helps prevent recurrence. On Monday morning when I go back to my clinical practice, I will feel more comfortable recommending neoadjuvant pembrolizumab to patients at risk for recurrence,” Dr Geynisman stated.