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.

Background: Kidney function assessment by estimated glomerular filtration rate (eGFR) equations, such as the Chronic Kidney Disease-Epidemiology Collaboration (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 versus non-Black patients. We aimed to characterise the effect of removing race from the CKD-EPI equation on dosing and eligibility of anticancer drugs with kidney function cutoffs.
Methods: We did a retrospective analysis of patients enrolled in phase 1 studies sponsored by the Cancer Therapy Evaluation Program between January, 1995, and October, 2010. eGFR based on creatinine (eGFR _Cr ) was calculated by the CKD-EPI equation and a version of the CKD-EPI equation without the race term (CKD-EPI _{without race} ). Estimated creatinine clearance (eCl _Cr ) was calculated by the Cockcroft-Gault equation. Dosing simulations based on each assessment of kidney function were done for ten anticancer drugs with kidney function cutoffs for dosing (oxaliplatin, capecitabine, etoposide, topotecan, fludarabine, and bleomycin) or eligibility (cisplatin, pemetrexed, bendamustine, and mitomycin) based on labelling approved by the US Food and Drug Administration or consensus guidelines. The absolute proportion of patients eligible or in each renal dosing range was calculated for each drug. Eligibility and dosing discordance rates were also calculated.
Findings: Demographics and laboratory values from 340 Black patients (172 men and 168 women) were used. Median age was 57 years (IQR 47-64), median bodyweight was 78·1 kg (67·0-89·8), median body surface area was 1·91 m ² (1·77-2·09), and median serum creatinine concentration was 0·9 mg/dL (0·8-1·1). Median eGFR _Cr or eCl _Cr was 103 mL/min (85-122) calculated by CKD-EPI, 89 mL/min (73-105) by CKD-EPI _{without race} , and 90 mL/min (72-120) by Cockcroft-Gault. Black patients were recommended to receive dose reductions or were rendered ineligible to receive drug more frequently when using CKD-EPI _{without race} than when using CKD-EPI, but at a similar rate as when using Cockcroft-Gault. The number of patients ineligible for therapy or recommended to receive any renal dose adjustment when CKD-EPI _{without race} versus CKD-EPI was used increased by 72% (from 25 of 340 to 43 of 340 patients) for cisplatin, by 120% (from five to 11) for pemetrexed, by 67% (from three to five) for bendamustine, by 150% (from ten to 25) for capecitabine, by 150% (from ten to 25) for etoposide, by 67% (from three to five) for topotecan, by 61% (from 74 to 119) for fludarabine, and by 163% (from eight to 21) for bleomycin. Up to 18% of patients had discordant recommendations using CKD-EPI _{without race} versus CKD-EPI.
Interpretation: 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.
Funding: National Institutes of Health.
Competing Interests: Declaration of interests MAC reports personal fees from AstraZeneca, outside the submitted work. JHB has received expert witness fees from Pfizer, and through his institute has received research support from AbbVie and Spectrum Pharmaceuticals, outside the submitted work; his spouse holds GlaxoSmithKline stocks. TDN reports personal fees from MediBeacon and CytoSorbents, and royalties from McGraw-Hill Education, outside the submitted work. SPI declares no competing interests.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)