Real-world survival outcomes and prognostic factors with adjuvant pembrolizumab for renal cell carcinoma.

Abstract

e16555 Background: The KEYNOTE-564 trial established adjuvant pembrolizumab as a standard of care for high-risk renal cell carcinoma (RCC) post-nephrectomy. We sought to validate these findings in a real-world setting and identify clinical prognostic factors within a large, multi-institutional cohort. Methods: We conducted a retrospective cohort study in Epic COSMOS, identifying the largest-to-date RCC cohort undergoing nephrectomy who received post-nephrectomy adjuvant pembrolizumab. The study period spanned from the FDA approval date (Nov 17, 2021) to Dec 20, 2025, ensuring at least one month of follow-up prior to the query date. Overall survival (OS) was estimated using the Kaplan–Meier method. Univariate Cox proportional hazards models with false discovery rate (FDR) correction were used to evaluate factors associated with OS and systemic therapy–free survival (STFS) (time to post-adjuvant systemic therapy initiation, used as a proxy for metastatic disease). Results: Among 2,656 patients, the median age was 64 years, 67.8% were male, and 75 deaths occurred during follow-up. The real-world OS rates at 12, 24, 36, and 48 months were 98.2%, 96%, 94%, and 93.5%, respectively, and were comparable to the OS reported in KEYNOTE-564. Worse OS was significantly associated with increasing age (HR: 1.05 [1.03-1.07], FDR < 0.01) and the Charlson comorbidity index (HR: 1.19 [1.11-1.28], FDR < 0.01). Gender and BMI had no impact on OS. Regarding laboratory biomarkers, protective effects on OS were observed for Hemoglobin (HR: 0.73 [0.64-0.83], FDR < 0.01), RBC count (HR: 0.40 [0.27-0.58], FDR < 0.01), MCHC (HR: 0.77 [0.68-0.87], FDR < 0.01), lymphocyte-to-monocyte ratio (HR: 0.74 [0.61-0.90], FDR = 0.01), Albumin (HR: 0.31 [0.18-0.53], FDR < 0.01), and Total Bilirubin (HR: 0.24 [0.07-0.80], FDR = 0.04). Conversely, worse OS was associated with high eosinophil-to-lymphocyte ratio (HR: 4.84 [2.14-10.91], FDR < 0.01), Monocytes (HR: 3.20 [1.34-7.59], FDR = 0.02), WBC (HR: 1.11 [1.03-1.95], FDR = 0.02), and RDW (HR: 1.11 [1.02-1.21], FDR = 0.03). Initiation of subsequent systemic therapy occurred in 232 (8.7%) patients and was associated with significantly worse OS (HR: 3.96 [2.48–6.34]; p < 0.001). For STFS, shorter time to systemic therapy was significantly associated with higher baseline RDW (HR: 1.12 [1.07-1.17], FDR < 0.01), whereas longer STFS was significantly associated with higher hemoglobin (HR: 0.86 [0.79-0.93], FDR < 0.01), and MCHC (HR: 0.87 [0.79-0.94], FDR = 0.01). Conclusions: The real-world OS after adjuvant pembrolizumab following nephrectomy for RCC was comparable to the trial. Comorbidity burden and baseline laboratory variables were associated with outcomes and may support real-world risk stratification.