Risk of severe toxicity from topical fluoropyrimidine treatment in patients carrying DPYD variant alleles.

Authors

null

Javier Granados

University of Michigan, Ann Arbor, MI

Javier Granados , Amy Pasternak , Norah Lynn Henry , Vaibhav Sahai , Daniel Louis Hertz

Organizations

University of Michigan, Ann Arbor, MI, University of Michigan Rogel Comprehensive Cancer Center, Ann Arbor, MI, University of Michigan College of Pharmacy, Ann Arbor, MI

Research Funding

No funding received
None.

Background: Patients carrying variant alleles of DPYD that reduce activity of dihydropyrimidine dehydrogenase have unacceptably high risk of severe toxicity from systemic fluoropyrimidine chemotherapy. DPYD testing prior to systemic fluoropyrimidine treatment is standard of care across Europe and is increasingly used in USA. There is a published case report of fatal toxicity from topical fluoropyridine chemotherapy in a DPYD variant carrier, but the risk of severe toxicity in these patients is unknown. This information is critical to determine whether patients receiving topical fluoropyrimidine treatment should also undergo DPYD genetic testing. The objective of this retrospective cohort study was to determine whether patients carrying DPYD variant alleles have increased risk of severe toxicity from topical fluoropyrimidine treatment. Methods: Individuals who received topical fluoropyrimidine treatment at Michigan Medicine and had available DPYD genotype data, due to participation in the Michigan Genomics Initiative institutional genetic data repository, were eligible for this analysis. Clinical data for the first cycle of topical fluoropyrimidine treatment was abstracted from the electronic medical record by an investigator blinded to genetic data. Toxicities were graded based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoint was grade 3+ toxicity. The secondary endpoint was grade 1+ toxicity. Genotypes for five validated decreased- or null-activity DPYD variant alleles were included: DPYD*2A (rs3918290), DPYD*13 (rs55886062), DPYD p.D949V (rs67376798) DPYD HapB3 (rs56038477) and DPYD p.Y186C (rs115232898). Toxicity rates in DPYD variant carriers vs. wild-type were compared using Fisher’s Exact tests. Results: 201 patients receiving topical fluoropyrimidine therapy who had available DPYD genotype data were included in the analysis. Most patients were self-reported white (97%), male (71%), and received topical fluoropyrimidine for a diagnosis of actinic keratosis (79%). As expected in a US patient cohort, 7.0% (14/201) of patients carried a DPYD variant. No patients experienced grade 3+ toxicity. Patients carrying a DPYD variant allele had nominally higher risk of grade 1+ toxicity (21.4% vs. 10.2%, odds ratio = 2.40 (95% Confidence Interval: 0.10-2.53), p = 0.19). Conclusions: Patients carrying DPYD variant alleles may have increased risk of non-severe toxicity from topical fluoropyrimidines, but the risk of severe toxicity is minimal regardless of genotype. DPYD genetic testing to prevent severe and fatal fluoropyrimidine toxicity should be reserved for patients receiving systemic treatment and need not include patients receiving topical treatment, in whom risk of severe toxicity is minimal.

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Symptoms and Survivorship

Track

Symptom Science and Palliative Care

Sub Track

Palliative Care and Symptom Management

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 12123)

DOI

10.1200/JCO.2023.41.16_suppl.12123

Abstract #

12123

Poster Bd #

491

Abstract Disclosures

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