In a study reported in The Lancet Oncology, Casal et al showed that removing race as a factor in the Chronic Kidney Disease–Epidemiology Collaboration (CKD-EPI) equation for estimated glomerular filtration rate (eGFR) would result in calculation of a lower eGFR in Black patients. This might result in more of these patients being considered ineligible to receive cancer therapies—or needing dose adjustments for those therapies—associated with kidney function requirements.
As stated by the investigators, “Kidney function assessment by eGFR equations, such as the CKD-EPI equation, is important to determine dosing and eligibility for anticancer drugs. Inclusion of race in eGFR equations calculates a higher eGFR at a given serum creatinine concentration for Black patients vs non-Black patients. We aimed to characterize the effect of removing race from the CKD-EPI equation on dosing and eligibility [for] anticancer drugs with kidney function cutoffs.”
Study Details
The study was a retrospective analysis of data from patients enrolled in phase I studies sponsored by the Cancer Therapy Evaluation Program between January 1995 and October 2010. eGFR based on creatinine (eGFRCr) was calculated using the CKD-EPI equation and a version of the equation excluding the race term (CKD-EPI–without race). Estimated creatinine clearance was calculated by the Cockcroft-Gault equation.
Dosing simulations based on each assessment were performed for 10 anticancer drugs with kidney function cutoffs for dosing (oxaliplatin, capecitabine, etoposide, topotecan, fludarabine, and bleomycin) or eligibility (cisplatin, pemetrexed, bendamustine, and mitomycin) based on U.S. Food and Drug Administration labeling or consensus guidelines.
Removing race from the CKD-EPI equation will calculate a lower eGFR for Black patients and exclude more patients from receiving anticancer therapy, which could lead to undertreatment of Black patients with cancer and adversely affect their outcomes….— Casal et al
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Key Findings
Data from 340 Black patients (172 men and 168 women) were used in the analysis. Median age was 57 years (interquartile range [IQR] = 47–64 years); median body weight was 78.1 kg (IQR = 67.0–89.8 kg); median body surface area was 1.91 m² (IQR = 1.77–2.09 m2); and median serum creatinine concentration was 0.9 mg/dL (IQR = 0.8–1.1 mg/dL).
Median eGFRCr or estimated creatinine clearance was 103 mL/min (IQR = 85–122 mL/min) calculated by CKD-EPI, 89 mL/min (IQR = 73–105 mL/min) by CKD-EPI–without race, and 90 mL/min (IQR = 72–120 mL/min) by Cockcroft-Gault.
Patients were recommended to receive dose reductions or were rendered ineligible to receive treatment more frequently when using CKD-EPI–without race vs CKD-EPI, whereas rates were similar between the Cockcroft-Gault equation and CKD-EPI–without race.
The number of patients ineligible for therapy when CKD-EPI–without race vs CKD-EPI was used increased from 25 to 43 (72% increase) for cisplatin, from 5 to 11 (120% increase) for pemetrexed, and from 3 to 5 (67% increase) for bendamustine.
The number of patients recommended to receive any renal dose adjustment when CKD-EPI–without race vs CKD-EPI was used increased from 0 to 2 patients for oxaliplatin, from 10 to 25 (150% increase) for capecitabine, from 10 to 25 (150% increase) for etoposide, from 3 to 5 (67% increase) for topotecan, from 74 to 199 (61% increase) for fludarabine, and from 8 to 21 (163% increase) for bleomycin.
Across all treatments, drug eligibility discordance ranged from 1% to 5% for CKD-EPI vs CKD-EPI–without race and from < 1% to 5% for Cockcroft-Gault vs CKD-EPI–without race. Dose adjustment discordance ranged from 1% to 18% for CKD-EPI vs CKD-EPI–without race and from < 1% to 15% for Cockcroft-Gault vs CKD-EPI–without race.
The investigators concluded, “Removing race from the CKD-EPI equation will calculate a lower eGFR for Black patients and exclude more patients from receiving anticancer therapy, which could lead to undertreatment of Black patients with cancer and adversely affect their outcomes…. This finding underscores the crucial impact that the choice of GFR-estimating equation, including whether or not to include race in the calculation, has on drug eligibility and dosing in Black patients with cancer.”
Thomas D. Nolin, PharmD, of the Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Institutes of Health. For full disclosures of the study authors, visit thelancet.com.
