Dr Voss on the Clinical Significance of the KEYNOTE-564 Study in ccRCC

Martin H. Voss, MD, genitourinary medical oncologist, clinical director, Genitourinary Medical Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the clinical significance of the phase 3 KEYNOTE-564 trial (NCT03142334) in patients with clear cell renal cell carcinoma (ccRCC).

KEYNOTE-564 stands as a landmark study in the treatment of patients with kidney cancer, marking a significant paradigm shift by bringing immunotherapy into the adjuvant setting, Voss begins. This trial represents a crucial advancement, as it moved PD-1 inhibition earlier in the course of disease management, he says. The study was conducted globally and was placebo controlled, he reports. It enrolled patients with ccRCC deemed at high risk for disease recurrence after complete resection of their primary tumors, with or without resectable metastatic sites. These patients were randomly assigned to receive either pembrolizumab (Keytruda) or placebo for up to 1 year, following a double-blind design, Voss explains, stating that the trial included stratification for certain risk factors and geographic areas to ensure comprehensive evaluation across diverse populations.

He continues by stating that this trial met its primary end point of disease-free survival. The first interim analysis showed a clear benefit in the pembrolizumab arm over the placebo arm. Over time, the data have matured, and the study’s sample size allowed for further analysis, particularly the statistical significance of overall survival (OS) as a key secondary end point, Voss emphasizes. After a median of 57.2 months of follow-up, the subsequent analysis confirmed a significant OS benefit with pembrolizumab vs placebo, which resulted in a second publication in The New England Journal of Medicine in April 2024, he notes.

The study reported a 5.2% improvement in OS with pembrolizumab vs placebo, a significant achievement since this trial is the only study of a PD-1 inhibitor to show an OS benefit compared with placebo in the adjuvant setting for kidney cancer, Voss explains. This breakthrough has had ripple effects across the oncology field, influencing discussions and shaping clinical practice on a global scale, he concludes.