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Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.

Risk of treatment-related death in carriers of pathogenic DPYD polymorphisms treated with fluoropyrimidine chemotherapy: A systematic review and patient-level analysis.


Gastrointestinal (Colorectal) Cancer

2019 ASCO Annual Meeting

Abstract No:

J Clin Oncol 37, 2019 (suppl; abstr e15132)

Author(s): Karan Rai, Bhavina D O Batukbhai, Gabriel A. Brooks; Geisel School of Medicine, Lebanon, NH; Dartmouth Hitchcock Medical Center, Lebanon, NH; Norris Cotton Cancer Center, Lebanon, NH

Abstract Disclosures


Background: Polymorphisms of the DPYD gene are present in 3-5% of the population and are associated with increased risk for grade ≥3 toxicity during treatment with fluoropyrimidine (FP) chemotherapy. Fatal toxicities in carriers of DPYD polymorphisms have been described in published reports, however reliable estimates of the risk of treatment-related mortality are lacking. Methods: We conducted a systematic review of the MEDLINE database to identify relevant manuscripts published before January 28, 2018. We searched for published studies of patients receiving standard-dose FP chemotherapy (5-fluorouracil or capecitabine) who had pre-treatment testing for ≥1 of 4 pathogenic DPYD polymorphisms (c.1236G > A/HapB3, c.1679T > G, c.1905+1G > A/*2A, and c.2846A > T) and who were systematically assessed for treatment-related toxicities. In the case of retrospective studies, we required that the cohort be defined by pretreatment characteristics (e.g., patients were not included on the basis of observed toxicity). Two reviewers extracted study- and patient-level data, with discrepancies resolved by consensus. The pooled data were analyzed to estimate the risk of treatment-related mortality among polymorphism carriers. Results: Of the 1290 references screened, 37 publications were included in the final analysis. Patient-level data identified 485 of 14,377 patients (3.4%) with pathogenic DPYD polymorphisms. There were 12 deaths among polymorphism carriers, resulting in a 2.5% risk of treatment-related mortality (95% CI 1.3-4.4%). Only 2 treatment-related deaths were reported in 13,892 patients without identified polymorphisms. Risk of death by genotype is shown in the table; two decedents were compound heterozygotes. Conclusions: Patients with pathogenic DPYD polymorphisms who are treated with standard-dose FP chemotherapy are at significant risk of death and can be prospectively identified through pharmacogenetic testing.

c.1236G > A/HapB3c.1679T > Gc.1905+1G > A/*2Ac.2846A > T
Patients tested3732841312,4248818
Deaths among carriers1166
Risk of death in carriers0.5%6.3%3.6%5.1%

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