The phase III KEYNOTE-564 study has reported that adjuvant pembrolizumab provides a significant improvement in overall survival for patients with clear cell renal cell carcinoma at high risk of recurrence after surgery. This study is significant, as it represents the first phase III study to show improved overall survival with any adjuvant therapy in kidney cancer. The research was presented by Toni K. Choueiri, MD, FASCO, and colleagues at the 2024 ASCO Genitourinary Cancers Symposium (Abstract LBA359).
Toni K. Choueiri, MD, FASCO
About KEYNOTE-564
The KEYNOTE-564 study was a randomized, multicenter, double-blind trial designed to evaluate the efficacy of pembrolizumab as an adjuvant therapy in patients with clear cell renal cell carcinoma. A total of 994 patients were randomly assigned 1:1 to receive either pembrolizumab (n = 496) or placebo (n = 498). Patients were aged 18 years or older, had clear cell renal cell carcinoma (with or without sarcomatoid features, which would indicate a highly aggressive form of cancer) that was at intermediate-high or high risk of recurrence, had received no prior therapy for kidney cancer, and underwent surgery ≤ 12 weeks before starting the trial.
The primary endpoint of the study was disease-free survival. Secondary endpoints included safety and overall survival.
Key Findings
Patients had a median follow-up time of approximately 57 months, with the range spanning from 47.9 to 74.5 months. At 48 months, the estimated overall survival rate was 91.2% for the pembrolizumab group vs 86.0% for the placebo group.
Patients who received pembrolizumab had a 28% reduction in the risk of their cancer recurring when compared to patients who received placebo. In addition, patients who received pembrolizumab had a 38% lower risk of death compared to patients in the placebo group. The study showed benefits across various patient subgroups.
The side effects experienced by patients in the KEYNOTE-564 study were predominantly autoimmune in nature, affecting various organs, consistent with what is generally observed with PD-1 inhibitors. Around 18% of the patients discontinued pembrolizumab due to these side effects, but no fatalities were directly linked to the treatment.
“Through this study, we now understand that pembrolizumab is more than just a measure to delay recurrence in kidney cancer; it is a means to significantly improve overall survival for patients,” said lead study author Dr. Choueiri, Director of the Lank Center for GU Oncology at Dana-Farber Cancer Institute. “Considering that many patients with clear cell renal cell carcinoma have a high risk of recurrence leading to [incurable] distant metastases, this finding is practice-changing.”
Next Steps
Building on the success of pembrolizumab in the KEYNOTE-564 study, the researchers are now recruiting patients for a new trial that combines pembrolizumab with the hypoxia-inducible factor (HIF)-2α inhibitor belzutifan.
ASCO Expert Perspective
“The KEYNOTE-564 study's update, highlighting pembrolizumab's efficacy in the adjuvant setting post–kidney cancer surgery, marks a significant development in treatment protocols. By confirming improvements in both disease-free and overall survival, the study positions pembrolizumab as a standard care option for high-risk patients,” said Mark T. Fleming, MD, ASCO Expert.
Disclosure: The study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit coi.asco.org.
