Impact of Renal Function Eligibility Criteria on Clinical Trials and Real-World Survival Outcomes Among Patients With Metastatic Renal Cell Carcinoma

BACKGROUND: Registration trials of first-line (1L) therapies in metastatic renal cell carcinoma (mRCC) employed strict renal function criteria, which may not reflect real-world patients. We evaluated the impact of trial-based renal function eligibility criteria on real-world outcomes.

METHODS: Using a nationwide, deidentified electronic health record-derived database, we included patients diagnosed with mRCC between January 2011 and April 2023 who received 1L systemic therapy. Renal function criteria were based on trial protocols and included serum creatinine (≤1.5 vs >1.5 x upper limit of normal), estimated glomerular filtration rate (≥30 vs <30 mL/min/1.73 m 2), and calculated creatinine clearance (≥40 vs <40 mL/min). Outcomes were real-world progression-free survival (rwPFS) and overall survival (rwOS) from 1L. Statistical analyses included inverse probability of treatment weighted Kaplan-Meier methods and Cox proportional hazard models with multiple imputation.

RESULTS: Among 6896 patients, 4647 (67.4%) met all renal function criteria (Included), 586 (8.5%) met at least one (Relaxed), 174 (2.5%) met none (Excluded), and 1489 (21.6%) had unknown renal function (Unknown). In adjusted analyses, patients in the Relaxed and Excluded groups combined had a lower median rwPFS (hazard ratio [HR], 1.12; 95% CI, 1.00-1.25) and rwOS (HR, 1.23, 95% CI, 1.08-1.39) than those in the Included group.

CONCLUSION: Patients who met all renal function criteria had better survival outcomes than those who did not, suggesting that clinical trial results for mRCC may not be fully generalizable to real-world patients.