Post Hoc Analysis Confirms DFS Benefit of Adjuvant Pembrolizumab in Patients With ccRCC

Results of the phase 3 KEYNOTE-564 study demonstrated the efficacy of adjuvant pembrolizumab for patients with clear cell renal cell carcinoma (ccRCC) and increased risk of recurrence after nephrectomy by prolonging disease-free survival (DFS) compared with placebo.

At the 24th Annual Meeting of the Society of Urologic Oncology, Dr. Tian Zhang, of UT Southwestern Medical Center, presented the results of a post hoc exploratory analysis on DFS in patient subgroups from the trial, based on the UCLA Integrated Staging System (UISS) risk groups and disease stage.

During the KEYNOTE-564 study, 994 patients with ccRCC were assigned 1:1 to receive either intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 17 cycles. UISS risk groups were obtained retrospectively from TNM stage, Fuhrman nuclear grade, and Eastern Cooperative Oncology Group performance status (ECOG PS). UISS groups were organized into intermediate risk (pT2, grade 4, N0, M0; pT3, grade 1, N0, M0; or pT3, grades 2-4, N0, M0, ECOG PS of 0), high risk (pT3, grades 2-4, N0, M0, ECOG PS of 1; pT4, any grade, N0, M0; or N1, M0), or M1 with no evidence of disease (NED).

The median follow-up was 30.1 months (range, 20.8-47.5 months). Most patients were UISS intermediate risk (n=732 [73.6%]; pembrolizumab, n=359; placebo, n=373), while 195 patients were UISS high risk (19.6%; pembrolizumab, n=100; placebo, n=95) and 58 patients had M1 NED (5.8%; pembrolizumab, n=29; placebo, n=29).

DFS rates were higher in the pembrolizumab arm of the trial in the UISS intermediate (hazard ratio [HR], 0.65; 95% CI, 0.48-0.88; 24-month rate: 81.5% vs 72.4%) and high risk (HR, 0.77; 95% CI, 0.49-1.20; 24-month rate: 65.0% vs 55.9%) groups, as well as the M1 NED group (HR, 0.28; 95% CI, 0.12-0.66; 24-month rate: 78.4% vs 37.9%). Across all patient subgroups, pembrolizumab offered a higher DFS rate over placebo.

Similar to results from the intention-to-treat population, adjuvant pembrolizumab was favored over placebo for its benefit of prolonging DFS in all patient subgroups based on UISS risk group and disease stage. These results further support the use of adjuvant pembrolizumab as a standard of care treatment in patients with ccRCC who are at increased risk of recurrence after nephrectomy.