Many Black patients would lose eligibility for anticancer medications or have a full dosage reduced if race were removed from the 2009 Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation for estimating glomerular filtration rate (eGFR) based on serum creatinine, according to investigators.
Inclusion of race in the CKD-EPI equation results in an approximately 16% higher eGFR (in mL/min/1.73 m2) at a given serum creatinine level for Black patients compared with non-Black patients of the same age and sex, Thomas D. Nolin, PharmD, of the University of Pittsburgh School of Pharmacy in Pittsburgh, Pennsylvania, and colleagues explained in The Lancet Oncology. They simulated cancer therapy use among 340 Black patients enrolled in National Cancer Institute phase 1 clinical trials from 1995 to 2010 using race-free kidney function equations. Median eGFR was 103 using the race-based CKD-EPI equation, 89 using the CKD-EPI equation without race, and 90 using the Cockcroft-Gault equation for creatinine clearance, another common formula used in oncology.
The investigators determined eligibility for 4 chemotherapy agents with kidney function cutoffs using the race-based CKD-EPI equation versus the race-free CKD-EPI and Cockcroft-Gault equations. Cisplatin ineligibility (eGFR less than 60) increased from 7% to 13% of patients, respectively. Pemetrexed ineligibility (eGFR less than 45) increased from 1% to 3%, respectively. Mitomycin ineligibility (eGFR less than 30) increased from 0% to 1% or less, respectively. Endamustine ineligibility (eGFR less than 40) increased by a few patients but remained at 1% across groups.
The investigators also found that the race-free formulas resulted in higher proportions of patients requiring dose reductions of 6 anticancer drugs. Oxaliptan dose reduction for an eGFR of less than 30 increased from 0% to 1% of patients. Capecitabine dose reduction for an eGFR of 30 to 50 increased from 3% to 7% of patients, and ineligibility (less than 30) from 0% to 1% or less. Etoposide dose reduction for an eGFR of 15-50 increased from 3% to 7% of patients. Topotecan dose reduction was required by a few more patients but the proportion held at 1%. Fludarabine dose reduction for an eGFR of 30 to 79 increased from 21% to 34% of patients, and ineligibility (eGFR less than 30) from 0% to 1% or less. Bleomycin dose reduction for an eGFR of less than 50 increased from 2% to 6% of patients.
“Black patients experience disparities in both cancer incidence and mortality, and are therefore especially susceptible to disease undertreatment,” Dr Nolin’s team noted. “Removal of race from GFR-estimating equations could lead to higher rates of anticancer drug exclusion, dose reduction, and disease undertreatment in Black patients with cancer, and thus could adversely affect survival outcomes.” They likewise acknowledged the possibility that Black patients might be overtreated and at risk for drug toxicity.
Until race-agnostic equations can be validated and implemented, a pragmatic and patient-centered approach should be used, the investigators suggested. Such an approach should be guided by “clinical judgment, individualised patient care, and a thorough understanding of the limitations of the various GFR-estimating equations.”
A joint National Kidney Foundation-American Society of Nephrology task force is currently reassessing the inclusion of race in eGFR equations.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Casal MA, Ivy SP, Beumer JH, Nolin TD. Effect of removing race from glomerular filtration rate-estimating equations on anticancer drug dosing and eligibility: a retrospective analysis of National Cancer Institute phase 1 clinical trial participants. Lancet Oncol. Published online August 13, 2021. doi:10.1016/S1470-2045(21)00377-6
Levey AS, Powe NR. eGFR and chemotherapy: will removing race create disparities? Lancet Oncol. Published online August 13, 2021. doi:10.1016/S1470-2045(21)00391-0