Could Nixing Race-Adjustments for eGFR Harm Black Cancer Patients?

Removing race from estimated glomerular filtration rate (eGFR) equations would result in fewer Black patients being eligible for certain anticancer drugs, researchers have demonstrated.

Their analysis showed that for Black patients, removing race from the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation reduced median eGFR from 103 mL/min to 89 mL/min. In addition, removing the race factor doubled the percentage of black patients with an eGFR under 60 mL/min — a clinically relevant cut-off below which many drugs have recommended changes to dosage and eligibility, reported Thomas D. Nolin, PharmD, PhD, of the University of Pittsburgh School of Pharmacy, and colleagues

Writing in The Lancet Oncology, the group suggested that the proportion of patients who would be ineligible to receive a drug, or would be recommended a dose reduction, increased anywhere from 61% to 163%, depending on the treatment type.

The CKD-EPI equation includes a race term that calculates a 15.9% higher eGFR for Black patients, reflecting higher measured eGFR in those patients of similar sex, age, and serum creatinine concentration. The inclusion of a race term has become relevant with the establishment of a task force by the National Kidney Foundation and the American Society of Nephrology to reassess the inclusion of race in diagnosing kidney issues.

“A race-agnostic equation for evaluating kidney function that is at least as accurate as CKD-EPI would be ideal,” said co-author Morgan A. Casal, PharmD, also of the University of Pittsburgh School of Pharmacy, in a press release. “Until such an equation is ready for widespread clinical implementation, physicians must take an individualised, patient-centered approach to evaluating kidney function when prescribing cancer pharmacotherapy. That includes fully recognizing the limitations and implications of the various GFR-estimating equations, such as whether or not race is included, especially if the resulting choice or dosage of drug can have a substantial impact on survival.”

Nolin and his colleagues performed a retrospective analysis of 340 Black patients enrolled in National Cancer Institute phase I studies between 1995 and 2010. Study participants’ kidney function was estimated using the CKD-EPI equation with and without race included. Estimates were generated using the Cockcroft-Gault equation, as well.

The team performed dosing simulations based on kidney function estimate for chemotherapies with kidney function cutoffs for dosing and eligibility.

They found increases in the number of patients ineligible for therapy or who would be recommended a dose reduction when race adjustments were removed from the CKD-EPI:

• 72% (from 25 to 43 patients) for cisplatin
• 120% (from 5 to 11) for pemetrexed (Alimta)
• 67% (from 3 to 5) for bendamustine (Bendeka, Treanda)
• 150% (from 10 to 25) for capecitabine
• 150% (from 10 to 25) for etoposide
• 67% (from 3 to 5) for topotecan
• 61% (from 74 to 119) for fludarabine
• 163% (from 8 to 21) for bleomycin

Up to 18% of patients had discordant dosing recommendations using CKD-EPI with race adjustments excluded versus CKD-EPI with race.

“Exclusion of the race term from the CKD-EPI equation could paradoxically worsen care for Black patients with cancer,” Nolin and his colleagues concluded. “Although guidance on implementation of new, race-agnostic methods of kidney function assessment is forthcoming, the timeline for widespread clinical implementation is unclear and omission of race from the CKD-EPI equation in the interim could negatively affect care for Black patients with cancer.”

In a commentary accompanying the study, Andrew S. Levey, MD, of Tufts Medical Center in Boston, and Neil R. Powe, MD, MPH, MBA, of the University of California San Francisco, wrote that while the omission of race from eGFR could have significant clinical implications for cancer chemotherapy, “adverse consequences for cancer outcomes could be minimized.”

They suggested eGFR should be the first step in evaluating GFR and noted that current guidelines recommend confirmatory testing if more accurate assessment is needed.

“More frequent use of confirmatory tests for GFR evaluation will increase effort and cost, but it will promote appropriate decisions and prevent disparities in cancer treatment,” they wrote.