Implementation and clinical benefit of DPYD genotyping in a Danish cancer population

Paulsen, Niels Herluf; Pfeiffer, Per; Ewertz, M.; Fruekilde, Palle Bach Nielsen; Feddersen, Søren; Holm, Hanne Spangsberg; Bergmann, Troels K.; Qvortrup, Camilla; Damkier, Per

doi:10.1016/j.esmoop.2023.100782

Cited by 6 publications

(9 citation statements)

References 22 publications

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“…Since our study was retrospective in nature and included a limited number of DPYD variant carriers, it is also possible that untested confounding factors have contributed to this unexpected result. Nevertheless, we did not have any fluoropyrimidine‐related deaths among this cohort of patients who underwent pharmacogenetic testing, consistent with other studies 26,33 …”

Section: Discussionsupporting

confidence: 90%

“…Patients with normal DPD had a higher, though non‐significant, incidence of hospitalizations and treatment interruptions when compared with DPYD variant carriers who had their doses reduced. The results of decreased hospitalizations among DPYD variant carriers corroborate other studies that documented reduced fluoropyrimidine‐related intolerance associated with DPYD‐ guided dose reduction 9,26,33 . While the finding of increased hospitalization and treatment interruption among those with normal DPD activity is deemed unexpected, a comparable finding of a higher incidence of treatment interruption in patients with normal DPD has been documented 26,33 .…”

Section: Discussionsupporting

confidence: 83%

“…Nevertheless, we did not have any fluoropyrimidine-related deaths among this cohort of patients who underwent pharmacogenetic testing, consistent with other studies. 26,33 Among patients who received irinotecan ± fluoropyrimidine, we found a non-significant higher percentage of unplanned hospitalization among UGT1A1 NM compared with UGT1A1 IM and PM. We did, however, find a non-significant higher percentage of irinotecan interruptions among UGT1A1 IM/UGT1A1 PM compared with UGT1A1 NM.…”

Section: Discussionmentioning

confidence: 74%

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Real‐world implementation of DPYD and UGT1A1 pharmacogenetic testing in a community‐based cancer center

Muldoon,

Beck,

Sebree

et al. 2024

Clinical Translational Sci

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We set out to demonstrate the feasibility of pharmacogenetic testing of DPYD and UGT1A1 and explore the clinical benefits in a community‐based cancer center. We conducted a retrospective review of 280 patients who underwent pharmacogenetic testing between November 2020 and May 2023. The primary end points included the percentage of patients with results prior to chemotherapy initiation, percentage of DPYD‐ and UGT1A1‐guided interventions implemented before chemotherapy initiation, and the turnaround time (TAT) for the pharmacogenetics results. Exploratory end points included a comparison of unplanned hospitalizations and treatment interruptions among (1) DPD phenotypes in patients who received fluoropyrimidines and (2) UGT1A1 phenotypes in patients who received irinotecan ± fluoropyrimidines. We evaluated cancer progression among patients who received DPYD‐guided dose reductions in the curative setting. More than 75% of patients had results prior to initiation of chemotherapy and 61.5% of the actionable interventions were implemented before chemotherapy, with a median TAT of 7 calendar days (IQR 5–8 calendar days). A non‐significant higher percentage of unplanned hospitalizations and treatment interruptions occurred among patients with normal DPYD compared with patients with DPYD‐guided dose reductions. A non‐significant higher frequency of treatment interruptions and dose reductions were observed in UGT1A1 intermediate metabolizer (IM) compared with UGT1A1 normal metabolizer (NM). None of the patients who received DPYD‐guided dose reductions in the curative setting experienced progression after a median follow‐up of 342 days. The real‐world evidence generated from this study demonstrates the feasibility of pre‐chemotherapy pharmacogenetic testing of DPYD and UGT1A1 in a community‐based cancer center.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 74%

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Real‐world implementation of DPYD and UGT1A1 pharmacogenetic testing in a community‐based cancer center

Muldoon,

Beck,

Sebree

et al. 2024

Clinical Translational Sci

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“…5 Implementation of PGx programs in oncology has led to reduced adverse events and improvement in outcomes. 12,108,109 Comprehensive medication management programs across diseases with PGx as a key component have shown improved outcomes and reductions in cost. 3,110,111 However, despite the evidence pointing to the clinical utility of PGx programs and successful implementation in other countries, 8,9 uptake in the United States remains dismally low.…”

Section: Infrastructure and Provider And Patient Education And Awarenessmentioning

confidence: 99%

“…11 For oncology patients, pretreatment testing for DPYD variants reduced the frequency of fluoropyrimidine-related hospitalization from 19% to 0%, and the number of toxicity-related deaths from 4.8% to 0%. 12 Another recent study showed that DPYD-guided fluoropyrimidine dosing did not negatively affect progressionfree survival and overall survival. 13…”

Section: Introductionmentioning

confidence: 99%

Overcoming Barriers to Discovery and Implementation of Equitable Pharmacogenomic Testing in Oncology

Shriver,

Adams,

McKelvey

et al. 2024

JCO

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Pharmacogenomics (PGx), the study of inherited genomic variation and drug response or safety, is a vital tool in precision medicine. In oncology, testing to identify PGx variants offers patients the opportunity for customized treatments that can minimize adverse effects and maximize the therapeutic benefits of drugs used for cancer treatment and supportive care. Because individuals of shared ancestry share specific genetic variants, PGx factors may contribute to outcome disparities across racial and ethnic categories when genetic ancestry is not taken into account or mischaracterized in PGx research, discovery, and application. Here, we examine how the current scientific understanding of the role of PGx in differential oncology safety and outcomes may be biased toward a greater understanding and more complete clinical implementation of PGx for individuals of European descent compared with other genetic ancestry groups. We discuss the implications of this bias for PGx discovery, access to care, drug labeling, and patient and provider understanding and use of PGx approaches. Testing for somatic genetic variants is now the standard of care in treatment of many solid tumors, but the integration of PGx into oncology care is still lacking despite demonstrated actionable findings from PGx testing, reduction in avoidable toxicity and death, and return on investment from testing. As the field of oncology is poised to expand and integrate germline genetic variant testing, it is vital that PGx discovery and application are equitable for all populations. Recommendations are introduced to address barriers to facilitate effective and equitable PGx application in cancer care.

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Antineoplastics

2023

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Implementation and clinical benefit of DPYD genotyping in a Danish cancer population

Cited by 6 publications

References 22 publications

Real‐world implementation of DPYD and UGT1A1 pharmacogenetic testing in a community‐based cancer center

Real‐world implementation of DPYD and UGT1A1 pharmacogenetic testing in a community‐based cancer center

Overcoming Barriers to Discovery and Implementation of Equitable Pharmacogenomic Testing in Oncology

Antineoplastics

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