Heterogeneity in methods for estimating renal function in anticancer drug development.

person Alexander B. Karol Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY info_outline Alexander B. Karol, Yu Fujiwara, Rodrigo Paredes, Anna Argulian, Himanshu Joshi, Matt D. Galsky

Authors person Alexander B. Karol Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY info_outline Alexander B. Karol, Yu Fujiwara, Rodrigo Paredes, Anna Argulian, Himanshu Joshi, Matt D. Galsky Organizations Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY, Roswell Park Comprehensive Cancer Center, Buffalo, NY, Mount Sinai Beth Israel, New York, NY, Icahn School of Medicine at Mount Sinai, New York, NY, Department of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY Abstract Disclosures Research Funding No funding sources reported Background: Accurate assessment of renal function is critical in oncology clinical trials. Many anti-cancer agents are renally excreted or cleared, and impaired kidney function can significantly impact drug safety and efficacy. In an effort to modernize renal eligibility criteria the American Society of Clinical Oncology–Friends of Cancer Research Organ Dysfunction Working Group recommended that if renal toxicity and clearance are not of direct treatment-related concern, then patients with impaired renal function should be included in trials (Lichtman, JCO , 2017). However, a diversity of approaches are available to determine renal function. Methods: We systematically searched the clinicaltrials.gov database to review renal eligibility criteria for phase III clinical trials. These trials evaluated systemic anti-cancer therapies in adult patients between October 28 th 2013, and October 28 th 2023. Studies were excluded if they did not include eligibility criteria related to renal function. The demographics of the trials and methods used for estimating renal function were recorded. Results: 436 trials met criteria for review and 231 trials, enrolling 111,424 patients, met our inclusion criteria. Systemic therapies explored included: immunotherapy (98 trials, 42%), targeted therapy (110 trials, 48%), chemotherapy (17 trials, 7%) or other regimens (6 trials, 3%). Renal function exclusion criteria are shown in the Table. Among studies that estimated renal function with a formula, 140 (61%) studies used Cockcroft-Gault, 3 (1%) used Modification of Diet in Renal Disease, 9 (4%) used an institutional standard, 10 (4%) used a heterogenous combination of estimation equations, and 69 (30%) trials did not specify the estimation approach. Conclusions: In phase III clinical trials involving adult cancer patients, there is substantial heterogeneity in methodologies utilized for determining renal function as related to trial eligibility. Harmonization of approaches to estimate renal function in oncology trials may improve trial accessibility, generalizability, and comparability. Approaches to estimate renal function. Renal Function Exclusion Criteria Number of Trials (%) Serum creatinine relative to upper limit of normal 30 (13%) Absolute serum creatinine, mg/dL 8 (3%) Creatinine clearance (CrCL) mL/min 87 (38%) Estimated glomerular filtration rate (eGFR), mL/min/1.73 m 2 3 (1%) Heterogenous combinations (i.e CrCL+eGFR) 87 (38%) Not specified 15 (7%)