An updated analysis of the Phase 3 KEYNOTE-564 trial (NCT03142334) found that adjuvant treatment with pembrolizumab (Keytruda) continued to demonstrate improved disease-free survival (DFS) compared to placebo in patients with renal cell carcinoma (RCC) at high risk of recurrence.1
The findings were reported by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School in Boston, Massachusetts at the 2022 Genitourinary Cancer Symposium in San Francisco, California.
Previously reported data from KEYNOTE-564 revealed that treatment with adjuvant pembrolizumab produced a statistically significant and clinically meaningful DFS benefit over placebo in the intent-to-treat population (HR: 0.68, 95% CI: 0 .53-0.87, P = 0.001).2 The 2022 GU Symposium presentation consisted of an updated analysis of efficacy and safety with 30.1 months of follow-up.
KEYNOTE-564 evaluated patients with RCC defined as intermediate to 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) and M1 no signs of disease (NED) after surgery. Patients were randomized 1:1 to receive either pembrolizumab 200 mg every 3 weeks (n=496) or placebo every 3 weeks (n=498).
The median age of patients was 60 years in the treatment and placebo groups. A total of 347 patients in the pembrolizumab group were male (70.0%) versus 359 patients (72.1%) in the placebo group. Regarding the risk category, 427 patients were at intermediate-high risk (86.1%), 40 patients (8.1%) were at high risk and 29 patients (5.8%) were M1 NED in the treatment group versus 433 (86.9%), 36 (7.2%), and 29 (5.8%) in the placebo group, respectively. In the treatment group, there were 52 patients (10.5%) in whom sarcomatoid features were present versus 414 patients (83.5%) in whom sarcomatoid features were absent versus 59 (11.8%) and 415 (83.3%) in the placebo group.
For the primary endpoint of DFS, benefit was maintained in patients receiving pembrolizumab (RR: 0.63, 95% CI: 0.50-0.80, nominal P
• Intermediate-high risk: RR, 0.68 (95% CI: 0.52-0.89)
• High risk: RR, 0.60 (95% CI: 0.33-1.10)
• M1 NED: RR, 0.28 (95% CI: 0.12-0.66)
“The estimated DFS rate at 24 months was 78.3% with pembrolizumab versus 67.3% with placebo…The estimated rate [overall survival] the 24-month rate was 96.2% with pembrolizumab versus 93.8% with placebo,” the authors wrote.
In the primary analysis of KEYNOTE-564, presented at 24.1 months follow-up, 470 patients (96.3%) in the pembrolizumab group experienced an all-cause adverse event (AE) versus 452 (91.1%) in the placebo group; in the updated results presented at the 2022 ASCO GU Symposium, the number of patients in the pembrolizumab arm experiencing an all-cause AE was unchanged compared to 453 patients (91.3%) in the placebo arm. Grade 3-4 AEs were also very similar in the pembrolizumab arm at 24.1 months and 30.1 months with 42 patients (8.6%) and 43 patients (8.8%) respectively, versus 3 patients (0 .6%) in the placebo arm at 24.1 months and 30.1 months. 30.1 months.
“I believe this updated analysis of KEYNOTE-564 further supports adjuvant pembrolizumab as a new standard of care for patients with RCC at high risk of recurrence,” Choueiri said. Urology time®.
1. Choueiri TK, Tomczak P, Park SH, et al. Pembrolizumab as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma: KEYNOTE-564 30-month follow-up results. J Clin Oncol. 2022;40(suppl 6):abstr 290. doi:10.1200/JCO.2022.40.6_suppl.290
2. Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab after nephrectomy in renal cell carcinoma. N Engl J Med. 2021;385(8):683-694. doi:10.1056/NEJMoa2106391