(UroToday.com) The 2025 ASCO annual meeting featured a kidney cancer rapid oral abstract session and a presentation by Dr. Naomi Haas discussing five-year follow-up results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab for the treatment of clear cell RCC. KEYNOTE-564 established pembrolizumab monotherapy as the first adjuvant regimen to significantly improve both disease free survival and overall survival versus placebo after surgery for patients with clear cell RCC at increased risk of recurrence.1 At the 2025 ASCO annual meeting, Dr. Haas and colleagues presented results from the fourth prespecified interim analysis with a minimum follow-up of 5 years.
KEYNOTE-564 is a randomized, double-blind, placebo controlled, phase 3 study, which enrolled adults with clear cell RCC with intermediate-high (pT2 Grade 4 or sarcomatoid, or pT3 any Grade, N0 M0) or high (pT4 any Grade, N0 M0, or any pT and Grade, N+ M0) risk of recurrence or M1 with no evidence of disease who had nephrectomy and/or metastasectomy ≤12 weeks prior to 1:1 randomization to pembrolizumab 200 mg or placebo IV every 3 weeks. Treatment continued for ~1 year (17 cycles) or until recurrence, intolerable adverse events, or physician decision to discontinue treatment. The trial design is as follows:
The primary endpoint was disease free survival by investigator, and the key secondary endpoint was overall survival. The study met its disease free survival and overall survival objectives at earlier analyses, thus no subsequent formal statistical testing occurred. Adverse events were collected for 30-90 days after treatment cessation, depending on severity, with serious treatment-related adverse events collected regardless of timing.
There was a total of 994 patients randomized to pembrolizumab (n = 496) or placebo (n = 498), with a median follow-up time to data cutoff date of September 25, 2024, of 69.5 months (range: 60.2−86.9). All patients completed or discontinued study treatment ≥3 years earlier. There were 188 disease free survival events in the pembrolizumab group and 241 in the placebo group that occurred: Median disease free survival was not reached versus 68.3 months, respectively (HR 0.71, 95% CI 0.59−0.86), and the estimated disease free survival rate at 5 years was 60.9% versus 52.2%:
Based on the subgroup analyses for disease free survival, there was a benefit for pembrolizumab across all subgroups:
There were 68 overall survival events in the pembrolizumab group and 99 in the placebo group that occurred. Median overall survival was not reached in both arms (HR 0.66, 95% CI 0.48−0.90), and the estimated overall survival rate at 5 years was 87.7% versus 82.3%, respectively:
Overall survival outcomes were also consistent across key subgroups, including by prespecified risk and sarcomatoid features:
Subsequent therapies among patients with documented recurrence were most commonly systemic therapy only, and most commonly a VEGF/VEGFR inhibitor:
No new serious treatment-related adverse events have been reported for ≥3 years:
Dr. Haas concluded her presentation discussing five-year follow-up results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab for the treatment of clear cell RCC with the following take home points:
- Adjuvant pembrolizumab continued to demonstrate improved disease free survival and overall survival versus placebo in participants with clear cell RCC after a minimum of 5 years of follow-up
- Diseases free survival and overall survival benefits of pembrolizumab remained consistent in the ITT population and across subgroups
- Subsequent therapy comprised local (surgery/radiation) and systemic treatment strategies
- No new serious treatment-related adverse events were reported in 3+ years
- Pembrolizumab is the only adjuvant therapy in RCC to improve overall survival. These long-term results continue to support its use as the standard of care for patients at increased risk of recurrence
Presented by: Naomi B. Haas, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.
Related content: Adjuvant Pembrolizumab Shows Sustained Survival Benefit in Renal Cell Carcinoma at 5 Years - Naomi Balzer-Haas
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