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. 2024 Sep 3;7(9):e2432475.
doi: 10.1001/jamanetworkopen.2024.32475.

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

Stephen P Hibbs  1 , Laura Aiken  2 , Kruti Vora  3 , Chibuzo Mowete  2   4   5 , Lauren E Merz  6   7 , Vanessa Apea  1   2 , J Mark Sloan  8 , Christopher S Lathan  6   7 , Gregory A Abel  6   7 , Andrew Hantel  6   7
Affiliations

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

Stephen P Hibbs et al. JAMA Netw Open. .

Erratum in

  • Error in Abstract, Results, and Supplement 1.
    [No authors listed] [No authors listed] JAMA Netw Open. 2024 Dec 2;7(12):e2456980. doi: 10.1001/jamanetworkopen.2024.56980. JAMA Netw Open. 2024. PMID: 39699902 Free PMC article. No abstract available.

Abstract

Importance: Absolute neutrophil counts (ANCs) are used to determine cancer clinical trial (CCT) eligibility and systemic anticancer therapy (SACT) dose modifications. Duffy null-associated ANC (DANC) is a nonpathologic phenotype associated with lower ANC and most frequently seen in individuals with African and Middle Eastern ancestry. It is unclear whether CCTs exclude or SACT regimens modify doses for individuals with ANC within the DANC reference range.

Objective: To investigate CCT exclusions and SACT dose modifications for ANC within the DANC reference range.

Design, setting, and participants: This cross-sectional study of contemporary CCTs and SACT regimens included adult, interventional, phase 3 CCTs for the 5 most prevalent cancers in the US and United Kingdom (prostate, breast, melanoma, colorectal, and lung cancers) testing SACTs with start dates between November 1, 2021, and November 1, 2023, and that were registered on ClinicalTrials.gov. Preferred curative-intent SACT regimens were listed in National Comprehensive Cancer Network guidelines.

Exposure: Cancer clinical trial exclusions and SACT regimen modifications.

Main outcome and measures: Proportions of CCTs that exclude and SACT regimens that modify doses for individuals with an ANC within the DANC reference range.

Results: For CCTs, 289 of 382 trials (75.7%) were eligible, of which 221 (76.5% [95% CI, 71.1%-81.2%]) excluded patients with ANC values within the DANC reference range. Colorectal CCTs had the highest (38 of 44 [86.4% (95% CI, 72.6%-94.8%)]) and prostate CCTs had the lowest (11 of 23 [47.8% (95% CI, 26.8%-69.4%)]) proportions of exclusions. Of CCTs testing cytotoxic chemotherapy, 116 of 142 (81.7% [95% CI, 74.3%-87.7%]) had exclusions; 93 of 123 (75.6% [95% CI, 67.0%-82.9%]) CCTs testing targeted therapies alone and 12 of 24 (50.0% [95% CI, 29.1%-70.9%]) testing hormonal therapies alone had exclusions. Among the 113 US- and UK-based trials, exclusions were present in 89 (78.8% [95% CI, 70.1%-85.9%]). Of 71 SACT regimens, 38 (53.5% [95% CI, 41.3%-65.5%]) included dose modifications for ANC values within the DANC reference range. Lung cancer regimens had the highest (23 of 31 [74.2% (95% CI, 55.4%-88.1%)]) and prostate cancer had the lowest (0 of 12 [0 (95% CI, 0%-26.4%)]) proportions of modifications. Regimens including chemotherapy had modifications in 32 of 44 (72.7% [95% CI, 57.2%-85.0%]); 11 of 20 (55.0% [95% CI, 31.5%-76.9%]) of targeted therapy regimens and 0 of 16 (0% [95% CI, 0%-20.6%]) of hormonal therapy regimens had modifications. Among regimens including chemotherapy and/or targeted therapy, modifications were present in 38 of 55 (69.1% [95% CI, 49.7%-73.2%]).

Conclusions and relevance: In this cross-sectional study, substantial proportions of CCTs excluded and SACT regimens modified doses for patients with ANCs in the DANC reference range. These practices structurally discriminate against patients of African and Middle Eastern ancestry. While determining optimal SACT dose modifications requires further study, CCT exclusion criteria should be revised.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Apea reported receiving personal fees from ViiV Healthcare, Gilead Sciences Inc, and Preventx outside the submitted work. Dr Sloan reported consulting for Nuvectis Pharma Inc and serving on the advisory boards of AstraZeneca and Novartis AG outside the submitted work. Dr Lathan reported receiving grant funding from Amgen Inc and serving on the expert advisory council for The Bristol Myers Squibb Foundation outside the submitted work. Dr Abel reported consulting for Novartis AG and receiving research support from the American Cancer Society in collaboration with Flatiron Health and a subaward from the National Cancer Institute to care.coach outside the submitted work. Dr Hantel reported spousal employment for Real Chemistry; serving on the advisory boards of AbbVie Inc, GSK PLC, AstraZeneca, Celgene Corporation, and Bristol Myers Squibb; consulting for Genentech Inc and Jazz Pharmaceutical plc; and serving on the speaker’s bureau for the American Journal of Managed Care outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. The Proportions of Cancer Clinical Trials That Excluded Patients for Absolute Neutrophil Counts (ANCs) Within the Duffy Null–Associated ANC Reference Range by Cancer Type and Type of Restriction
Bars representing individual cancer types show all trials including each cancer type (prostate [n = 23], melanoma [n = 28], breast [n = 97], colorectal [n = 44], and lung [n = 105]). Overall crude values are for unique trials (n = 289), and overall weighted values weight each cancer type equally and include duplicates across cancer types (n = 297).
Figure 2.
Figure 2.. The Proportions of Systemic Anticancer Therapy Regimen Dose Modifications That Excluded Patients for Absolute Neutrophil Counts (ANCs) Within the Duffy Null–Associated ANC Reference Range by Cancer Type and Type of Modification
Bars representing individual cancer types are mutually exclusive (lung [n = 31], colorectal [n = 11], breast [n = 14], melanoma [n = 3], and prostate [n = 12]) and summed for the overall crude result. The overall weighted result weights each cancer type equally prior to summing.
See this image and copyright information in PMC

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