Dr Haas on the Rationale for Evaluating Adjuvant Pembrolizumab in Clear Cell RCC

“KEYNOTE-564 looked specifically at [treatment with] pembrolizumab vs placebo. In KEYNOTE-564, [approximately] 1000 patients were enrolled, with [DFS per] investigators’ assessment being the primary end point. OS and safety were considered key secondary end points.”

Naomi B. Haas, MD, a professor of medicine at the Hospital of the University of Pennsylvania and the director of the Prostate and Kidney Cancer Program at the Abramson Cancer Center, detailed the rationale for evaluating adjuvant pembrolizumab (Keytruda) for the treatment of patients with clear cell renal cell carcinoma (ccRCC) in the phase 3 KEYNOTE-564 trial (NCT03142334).

Most prior trials in the ccRCC landscape included patients with pT2 high-grade disease, Haas began. However, she noted that there was some variability in select studies that permitted patients with all grades of disease. For example, the phase 3 PROSPER EA8143 trial (NCT03055013) was based solely on clinical histology, not pathologic histology, she explained. Notably, other trials were commonly based on pathologic histology because patients on these studies had already undergone kidney surgery and investigators had already established the pathologic staging, she added.

Furthermore, the design of KEYNOTE-564, among other similarly designed studies, had some differences compared with these previous studies, of which some evaluated the duration of therapy of only 6 months, or immune checkpoint inhibitor (ICI) combinations with CTLA-4 inhibitors, Haas continued. Nevertheless, the KEYNOTE-564 assessed the ICI pembrolizumab, which patients on the study were treated with for 1 year, compared with placebo, she noted. The study included patients with histologically confirmed ccRCC who had not previously received systemic therapy, underwent surgery 12 weeks or less before random assignment, had a postnephrectomy intermediate-high risk of recurrence, and had a postnephrectomy high risk of recurrence. Additionally, patients were required to have an ECOG performance status of 0 or 1. The median follow-up was 69.5 months (range, 60.2-86.9). Of note, patients were randomly assigned 1:1 to receive either pembrolizumab monotherapy for up to 17 cycles (n = 496) or placebo for up to 17 cycles (n = 498). The primary end point was disease-free survival; secondary end points included overall survival and safety.