Introduction:

In the phase 3 KEYNOTE-564 study (NCT03142334), adjuvant pembrolizumab prolonged disease-free survival (DFS) in patients with clear cell renal cell carcinoma (ccRCC) at increased risk of recurrence after nephrectomy compared with placebo (DFS at 24 months: 77.3% vs 68.1%; hazard ratio [HR] for recurrence or death, 0.68; 95% CI, 0.53-0.87; P=0.002). Continued DFS improvement with adjuvant pembrolizumab was observed after 30 months of follow-up. Results of a post hoc exploratory analysis of DFS in patient subgroups based on UCLA Integrated Staging System (UISS) risk groups and disease stage are reported.

Methods:

Patients with histologically confirmed ccRCC (pT2, grade 4 or sarcomatoid, N0, M0; pT3 or pT4, any grade, N0, M0; any pT, any grade, N+, M0; or M1 with no evidence of disease [NED]) were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 17 cycles (~1 year). DFS was assessed by investigator. UISS risk groups were derived retrospectively from TNM stage, Fuhrman nuclear grade, and Eastern Cooperative Oncology Group performance status (ECOG PS). UISS groups were 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 1; pT4, any grade, N0, M0; or N1, M0), or M1 NED. Other subgroups based on disease stage were also evaluated.

Results:

Baseline characteristics were generally balanced within subgroups. Median follow-up was 30.1 months (range, 20.8-47.5). Of 994 enrolled patients, most had UISS intermediate risk (n = 732 [73.6%]; pembrolizumab, n = 359; placebo, n = 373); 195 patients (19.6%; pembrolizumab, n = 100; placebo, n = 95) had UISS high risk, and 58 patients (5.8%; pembrolizumab, n = 29; placebo, n = 29) had M1 NED. DFS favored pembrolizumab versus placebo in the UISS intermediate-risk group (HR, 0.65 [95% CI, 0.48-0.88]; 24-month rate: 81.5% vs 72.4%), UISS high-risk group (HR, 0.77 [95% CI, 0.49-1.20]; 24-month rate: 65.0% vs 55.9%), and M1 NED group (HR, 0.28 [95% CI, 0.12-0.66]; 24-month rate: 78.4% vs 37.9%). DFS favored pembrolizumab versus placebo across all patient subgroups based on disease stage (Table).

Conclusion:

Consistent with the results of the intention-to-treat (ITT) population, adjuvant pembrolizumab prolonged DFS compared with placebo for all patient subgroups based on UISS risk groups and disease stage. Taken together with results in the ITT population, these results further support the use of adjuvant pembrolizumab as standard of care for patients with RCC at increased risk of recurrence after nephrectomy. ©2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 Genitourinary Cancers Symposium. All rights reserved.

Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA