Cancer Trial Eligibility and Therapy Modifications for Individuals With Duffy Null-Associated Neutrophil Count

Area of Science:

• Oncology and Hematology
• Clinical Trial Design
• Health Disparities

Background:

• Absolute neutrophil counts (ANCs) are critical for cancer clinical trial (CCT) eligibility and systemic anticancer therapy (SACT) dosing.
• Duffy null-associated ANC (DANC) is a nonpathologic, lower ANC phenotype common in individuals of African and Middle Eastern ancestry.
• The impact of DANC on CCT eligibility and SACT dose modifications remains unclear.

Purpose of the Study:

• To investigate the exclusion rates in CCTs for patients with ANCs within the DANC reference range.
• To examine SACT regimen dose modifications for patients with ANCs in the DANC reference range.

Main Methods:

• Cross-sectional study of adult, phase 3 CCTs for prevalent US/UK cancers (prostate, breast, melanoma, colorectal, lung) with start dates Nov 2021-Nov 2023.
• Analysis included CCT exclusion criteria and SACT regimen dose modification policies for ANC within the DANC reference range.
• Data sourced from ClinicalTrials.gov, with SACT regimens aligned with National Comprehensive Cancer Network guidelines.

Main Results:

• 75.7% of eligible CCTs excluded patients with ANCs in the DANC reference range.
• Colorectal and lung cancer trials showed the highest exclusion rates (86.4% and 81.7% respectively).
• 53.5% of SACT regimens included dose modifications for ANCs within the DANC reference range, with lung cancer regimens most frequently modified (74.2%).

Conclusions:

• Significant proportions of CCTs exclude patients and SACT regimens modify doses based on the DANC reference range.
• These practices create structural discrimination against patients of African and Middle Eastern ancestry.
• Revision of CCT exclusion criteria is recommended, while further study on optimal SACT dose modifications is needed.