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Potentially actionable pharmacogenetic variants and symptom control medications in oncology

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Abstract

Purpose

We estimated the prevalence of potentially actionable pharmacogenetic (PGx) variants related to symptom control medications (SCMs) based on institutional prescribing patterns and correlated presenting symptoms with SCM prescribing.

Methods

This was a retrospective study of adult ambulatory cancer patients undergoing electronic distress screening (EDS) within 90 days of intake to the cancer hospital. We estimated the proportion prescribed SCM(s) with PGx evidence within 90 days of intake. Those with potentially actionable variants were estimated using population frequency data from 1000 genomes. The expected number at risk of altered drug response was estimated. The associations between symptom scores and SCM(s) were estimated with logistic regression and threshold analyses performed with receiver operating characteristic (ROC) curves.

Results

Of 6985 patients, 3222 (46%) received ≥ one SCM. Of these, 2760 (86%) received SCM(s) with PGx evidence for CYP2B6, CYP2C19, CYP2D6, or SLC6A4; 2719 (84%) received a drug metabolized by CYP2D6, most commonly hydrocodone (40.4%), ondansetron (35.6%), oxycodone (24.2%), and/or tramadol (7.1%). Based on this, about one quarter were expected to have altered metabolism and/or drug response. One third were prescribed two or more SCMs with PGx evidence. About half reported at least one severe symptom, which significantly correlated with SCM prescribing (p < 0.001). Threshold scores were identified that highly correlated with SCM prescribing for anxiety, depression, nausea, neuropathy, pain, and sleep.

Conclusion

About half presented with significant symptom burden, which highly correlated with SCM prescribing. Most received SCMs with PGx evidence. Preemptive PGx testing for these variants should be evaluated in prospective trials to evaluate the impact on symptom control.

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Data availability

Most data are provided in the manuscript. Any additional data can be requested from the corresponding author.

Code availability

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Authors and Affiliations

  1. Department of Cancer Pharmacology & Pharmacogenomics, Atrium Health Levine Cancer Institute, 1021 Morehead Medical Drive, Charlotte, NC, 28204, USA

    Jai N. Patel, Elizabeth J. Jandrisevits, Issam S. Hamadeh & Ahmed Salem

  2. Department of Biostatistics, Atrium Health Levine Cancer Institute, Charlotte, NC, USA

    Danielle Boselli

  3. Section of Psycho-oncology, Center for Supportive Care and Survivorship, Atrium Health Levine Cancer Institute, Charlotte, NC, USA

    Patrick Meadors

  4. Department of Supportive Oncology, Atrium Health Levine Cancer Institute, Charlotte, NC, USA

    Declan Walsh

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  1. Jai N. Patel
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  2. Danielle Boselli
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  4. Issam S. Hamadeh
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  5. Ahmed Salem
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Contributions

JNP, IH, and AS were responsible for the conception and design of this manuscript. All authors contributed to the data collection, analysis, and manuscript preparation.

Corresponding author

Correspondence to Jai N. Patel.

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This study was approved by the Atrium Health Institutional Review Board. Waiver of consent was provided.

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Conflicts of interest

JNP serves as a consultant on the Clinical Advisory Council for VieCure, Inc. All remaining coauthors have no conflicts of interest to disclose.

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Patel, J.N., Boselli, D., Jandrisevits, E.J. et al. Potentially actionable pharmacogenetic variants and symptom control medications in oncology. Support Care Cancer 29, 5927–5934 (2021). https://doi.org/10.1007/s00520-021-06170-4

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  • DOI: https://doi.org/10.1007/s00520-021-06170-4

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