Dr Zhang on the Background of a KEYNOTE-564 Subgroup Analysis in RCC

Tian Zhang, MD, MHS, associate professor, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the background and results of subgroup analyses of the phase 3 KEYNOTE-564 (NCT03142334) in patients with renal cell carcinoma (RCC), highlighting the use of adjuvant pembrolizumab (Keytruda) in this patient population.

At the 2023 North American International Kidney Cancer Symposium, Zhang discussed findings from subgroup analyses of the use of the KEYNOTE-564 regimen in patients with high-risk RCC. KEYNOTE-564 compared the efficacy of adjuvant pembrolizumab vs placebo in patients with resected kidney cancer or those who exhibited oligometastatic disease post-nephrectomy, she begins. The core objective of these subgroup analyses was to discern patients with high-risk RCC who would derive optimal benefits from adjuvant pembrolizumab, Zhang states. Using the UCLA Integrated Staging System criteria, patients were delineated into intermediate vs high-risk vs M1NED populations. In these populations, investigators assessed the therapeutic advantage conferred by adjuvant pembrolizumab in KEYNOTE-564, Zhang adds.

It's noteworthy that pembrolizumab improved disease-free survival (DFS), the KEYNOTE-564 trial’s primary end point, across all stratified populations, she expands. The DFS benefit conferred by pembrolizumab in this trial supported the 2021 FDA approval of the agent for the treatment of patients with intermediate-high or high-risk RCC following nephrectomy or following nephrectomy plus metastatic lesion resection. Further subgroup analyses unveiled DFS nuances, indicating that patients harboring higher-risk disease manifestations, nodal involvement, M1NED status, or higher-grade tumors tended to exhibit more pronounced therapeutic responses to pembrolizumab, Zhang elucidates.

These findings underscore the correlation between the augmented risk of disease recurrence and the amplified therapeutic benefits conferred by adjuvant pembrolizumab across diverse patient cohorts, she continues. Thus, the study's delineation of patient subgroups has enhancedinvestigators’ understanding of differential patterns of response to pembrolizumab and outlined critical factors influencing the therapeutic efficacy of adjuvant pembrolizumab, thereby informing tailored treatment strategies for patients with kidney cancer undergoing adjuvant therapy, Zhang concludes.