ASCO 2025: Adjuvant Pembrolizumab Shows Sustained Benefit in ccRCC at 5 Years

The KEYNOTE-564 study (NCT03142334), a randomized, double-blind, placebo-controlled phase 3 trial, investigated pembrolizumab (Keytruda) as an adjuvant therapy for clear cell renal cell carcinoma (ccRCC) patients at increased risk of recurrence after surgery. This study has now presented results from its fourth prespecified interim analysis, with a minimum of 5 years of follow-up. Naomi Haas, MD, professor of medicine at the Abramson Cancer Center at the University of Pennsylvania, and investigator on KEYNOTE-564, discusses the study ahead of the 2025 American Society of Clincial Oncology (ASCO) Annual Meeting, where data from the 5-year follow-up is being presented.

A total of 994 patients were enrolled, with 496 receiving pembrolizumab and 498 receiving a placebo. The median follow-up time was 69.5 months. The study had previously met its primary endpoint of disease-free survival (DFS) and key secondary endpoint of overall survival (OS) in earlier analyses.

With this extended follow-up, the benefits of adjuvant pembrolizumab remain consistent. There were 188 DFS events in the pembrolizumab group compared to 241 in the placebo group. The median DFS was not reached for pembrolizumab vs 68.3 months for placebo, representing a 29% reduction in the risk of recurrence or death (HR 0.71; 95% CI, 0.59–0.86). The estimated 5-year DFS rate was 60.9% for pembrolizumab vs 52.2% for placebo.

For OS, there were 68 events in the pembrolizumab group and 99 in the placebo group. The median OS was not reached in either arm, with a 34% reduction in the risk of death (HR 0.66; 95% CI, 0.48–0.90). The estimated 5-year OS rate was 87.7% for pembrolizumab compared with 82.3% for placebo. These positive outcomes for both DFS and OS were consistent across all major subgroups, including those with different risk profiles and sarcomatoid features.

Importantly, no new serious treatment-related adverse events have been reported for over 3 years, reinforcing the safety profile observed in earlier analyses. The sustained efficacy and favorable safety profile continue to support adjuvant pembrolizumab as a standard-of-care option for ccRCC patients with an increased risk of recurrence after surgery.

REFERENCE:

Haas N, Powles T, Tomczak P, et al. Five-year follow-up results from the phase 3 KEYNOTE-564 study of adjuvant pembrolizumab (pembro) for the treatment of clear cell renal cell carcinoma (ccRCC). Presented at: 2025 ASCO Annual Meeting; May 30-June 3, 2025; Chicago, IL. Abstract 4514.