Metastatic progression and toxicity in high-risk clear cell renal cell carcinoma patients treated with adjuvant pembrolizumab at a tertiary care center.

471 Background: Pembrolizumab was approved in 2021 as adjuvant therapy for high-risk clear cell renal cell carcinoma (ccRCC) after benefit was shown in the KEYNOTE-564 (KN564) clinical trial. Limited institutional data are available to evaluate subsequent patient selection for adjuvant therapy, efficacy, or toxicity in broader clinical practice. This study assessed disease-free survival (DFS) and adverse events (AEs) among patients treated at a high-volume U.S. institution, using KN564 eligibility criteria. Methods: We included ccRCC patients who underwent nephrectomy from 2021 to present meeting high-risk criteria (pT2 grade 4, ≥pT3 any grade, N1, or M1 with no evidence of disease NED) in a prospective institutional database. Clinical characteristics were compared between adjuvant and surveillance cohorts. DFS was estimated using Kaplan–Meier methods; Cox regression adjusted for tumor grade, tumor size, and venous thrombus. AEs were graded by Common Terminology Criteria for Adverse Events (CTCAE). Results: Among 195 high-risk ccRCC patients, 134 (67%) were referred to medical oncology for adjuvant therapy. 72 (37%) received adjuvant pembrolizumab and 123 (63%) underwent surveillance with a median follow-up of 21 vs 15 months respectively (P=0.20, Table 1). Per KN564 criteria, within the surveillance cohort, 96 (78%) were M0 intermediate-to-high risk, 16 (13%) M0 high risk, and 11 (9%) M1 NED; corresponding proportions in the pembrolizumab group were 64 (89%), 5 (7%), and 3 (4%), respectively (P=0.28). Pembrolizumab improved DFS (adjusted HR 0.34; 95% CI 0.17–0.66; P = 0.001). Two-year DFS was 84% with pembrolizumab versus 65% with surveillance (absolute risk reduction 19%; number needed to treat = 6). Only 37/72 (51%) completed 12 months of pembrolizumab. Treatment-related AEs were the main cause for discontinuation: 41/72 (57%) experienced any grade AEs including 17/72 (24%) who experienced a grade 3 or 4 AE. The most common high-grade AEs included pneumonitis, dermatitis, acquired type 1 diabetes presenting with ketoacidosis, myocarditis, and colitis. Conclusions: In contemporary practice, adjuvant pembrolizumab confers a measurable DFS benefit for high-risk ccRCC. Serious adverse events occurred in 24% of patients and were a frequent reason for treatment discontinuation. These data provide further real-world evidence and support pragmatic, shared decision-making when considering adjuvant pembrolizumab. Disease-free survival and toxicity. Surveillance(N=123) Adjuvant Pembrolizumab(N=72) Median follow-up, months (IQR) 15 (5–31) 21 (11–28) 1-yr DFS 76% 91% 2-yr DFS 64% 84% DFS HR (95% CI) Ref 0.34 (0.17-0.66); P=0.001 2-yr Absolute Risk Reduction — 19% Any Grade AEs, % 41 (57) Grade 3–4 AEs, % — 17 (24) Number needed to treat to prevent 1 recurrence or death 6 Number experiencing an adverse event for 1 recurrence prevented — 3