A new analysis of KEYNOTE-564 demonstrates that
The updated analysis was presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium.
The study, which was led by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, Boston, found no increase in high-grade, or other, adverse events with 30 months of follow-up.
Pembrolizumab (Keytruda, Merck) is approved by the Food and Drug Administration in combination with axitinib, as a first-line treatment for patients with advanced renal cell carcinoma (RCC). The combination is also recommended by the European Society for Medical Oncology for advanced RCC.
KEYNOTE-564 is a phase 3, double-blind, multicenter trial of pembrolizumab versus placebo after surgery in participants with renal cell carcinoma. In previously presented interim KEYNOTE-564 results, the primary endpoint of disease-free survival for adjuvant pembrolizumab versus placebo was met in the intent-to-treat population (hazard ratio, 0.68; 95% confidence interval, 0.53-0.87; P = .001).
KEYNOTE-564 includes 994 patients (mean age, 60 years; 71% male) with confirmed clear cell RCC who were either intermediate to high risk, high risk, or M1 with no evidence of disease after surgery. All patients had surgery 12 or fewer weeks prior to randomization.
At 30.1 months, the disease-free survival difference in the intent-to-treat population between pembrolizumab and placebo at 78.3% versus 67.3% had a HR of 0.63 (95% CI, 0.50-0.80; nominal P < .0001), greater than the 77.3% versus 68.1% difference at 24.1 months (hazard ratio, 0.68, 95% CI, 0.53-0.87; P = .001).
Analysis of disease-free survival by recurrence risk subgroups showed an increasing benefit with increasing risk. In the intermediate- to high-risk group, the 24-month rates were 81.1% and 72.0% for pembrolizumab and placebo, respectively (HR, 0.68; 95% CI, 0.52-0.89). In the high-risk group, the 24-month rates were 48.7% and 35.4%, respectively (HR, 0.60; 95% CI, 0.33-1.10). In the M1 NED group, the rates were 78.4% and 37.9% for pembrolizumab and placebo, respectively (HR, 0.28; 95% CI, 0.12-0.66).
During a discussion about the presentation, Daniel M Geynisman, MD, of Fox Chase Cancer Center, Philadelphia, pointed to the respective absolute differences between pembrolizumab and placebo of 9% in the intermediate- to high-risk group, 13% in the high-risk group, and a “whopping difference of 41% in the M1 NED group,” but underscored that the M1 NED population represents only a small part of the trial population (5.8%). The same relationship was evident among sarcomatoid status subgroups, with 24-month absolute differences of 10.1% favoring pembrolizumab (HR, 0.63) with sarcomatoid features absent and 19.8% (HR, 0.54) when they were present.
Overall survival estimates showed an increasing benefit for pembrolizumab versus placebo (96.6% vs. 93.5%; HR, 0.54) at 24.1 months (96.2% vs. 93.8%, HR, 0.52), but this wasn’t statistically significance because the data collection was incomplete.
Between 24.1 months and 30.1 months, rates of treatment-related adverse events remained the same at 79.1% for pembrolizumab and 53.4% for placebo, with a treatment-related discontinuations in the pembrolizumab group at 17.6% and 18.6% at 24.1 and 30.1 months, respectively.
The study was funded by Merck Sharp & Dohme.