Reply to H.S. Hochster

Hertz, Daniel L

doi:10.1200/jco.23.00038

Cited by 3 publications

(2 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The actual carrier frequency in patients of European ancestry when considering the 4 germline variants that the FDA acknowledges have been validated is ~ 6%. 62 The FDA does not state what prevalence would be sufficient to justify DPYD testing, although it is notable that the FDA requires testing for the similarly common HLA-B*57:01 (allele frequency 6-7%) prior to abacavir treatment. 57 Even with a low prevalence (~ 6%) of DPYD IM or PM patients, based on the estimated 250,000 patients per year treated with FP in the United States, ~ 15,000 IM or PM patients annually receive FP treatment and are exposed to unacceptable risks of severe and fatal toxicity.…”

Section: Lack Of Recommendation To Screen Patients Prior To Fp Treatmentmentioning

confidence: 99%

“…Among the FDA's stated reasons for not recommending pretreatment DPYD testing was that the estimated prevalence of carrying a DPYD variant in White populations is 3–5%. The actual carrier frequency in patients of European ancestry when considering the 4 germline variants that the FDA acknowledges have been validated is ~ 6% 62 . The FDA does not state what prevalence would be sufficient to justify DPYD testing, although it is notable that the FDA requires testing for the similarly common HLA‐B*57:01 (allele frequency 6–7%) prior to abacavir treatment 57 .…”

Section: Response To the Fda's Recent Decisions Regarding Dpyd Testin...mentioning

confidence: 99%

See 1 more Smart Citation

Response to the FDA Decision Regarding DPYD Testing Prior to Fluoropyrimidine Chemotherapy

Hertz

Smith

Scott

et al. 2023

Clin Pharma and Therapeutics

Self Cite

View full text Add to dashboard Cite

Fluoropyrimidine (FP) chemotherapy is associated with severe, life‐threatening toxicities, particularly among patients who carry deleterious germline variants in the DPYD gene. Pretreatment DPYD testing is standard of care throughout most of Europe; however, it has not been recommended in clinical practice guidelines in the United States. Due to increased risk of severe toxicity, a Citizen's Petition asked the US Food and Drug Administration (FDA) to update language in FP drug labels to recommend DPYD testing as part of a boxed warning and recommend FP dose reduction in patients carrying deleterious germline variants. In response, the FDA updated the capecitabine package insert to inform patients about the toxicity risk and test availability and consider DPYD testing. However, the FDA did not include a testing recommendation or requirement, or a boxed warning. Additionally, the FDA did not recommend FP dose adjustment in DPYD variant carriers. This review provides a critical assessment of the DPYD‐FP pharmacogenetic association using the FDA's previously published Pharmacogenetic Pyramid, demonstrating that the evidence is compelling for recommending DPYD testing prior to FP treatment. Additionally, the FDA's stated concerns about recommending DPYD testing and DPYD‐guided FP dose adjustment are addressed and discussed in the context of the FDA's other genetic testing and dose adjustment recommendations. We call on the FDA to follow our European counterparts in recommending DPYD testing and genotype‐based dose adjustment to ensure patients with cancer receive safe and effective FP chemotherapy.

show abstract

Section: Lack Of Recommendation To Screen Patients Prior To Fp Treatmentmentioning

confidence: 99%

Section: Response To the Fda's Recent Decisions Regarding Dpyd Testin...mentioning

confidence: 99%

Response to the FDA Decision Regarding DPYD Testing Prior to Fluoropyrimidine Chemotherapy

Hertz

Smith

Scott

et al. 2023

Clin Pharma and Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

Strategies for DPYD testing prior to fluoropyrimidine chemotherapy in the US

Tracksdorf,

Smith,

Pearse

et al. 2024

Support Care Cancer

View full text Add to dashboard Cite

Strategies for DPYD Testing Prior to Fluoropyrimidine Chemotherapy in the United States

Tracksdorf,

Smith,

Pearse

et al. 2024

Preprint

View full text Add to dashboard Cite

Purpose Patients with dihydropyrimidine dehydrogenase (DPD) deficiency are at high risk for severe and fatal toxicity from fluoropyrimidine (FP) chemotherapy. Pre-treatment DPYD testing is standard of care in many countries, but not the United States (US). This survey assessed pre-treatment DPYD testing approaches in the US to identify best practices for broader adoption. Methods From August to October 2023, a 22-item QualtricsXM survey was sent to institutions and clinicians known to conduct pre-treatment DPYD testing and broadly distributed through relevant organizations and social networks. Responses were analyzed using descriptive analysis. Results Responses from 24 unique US sites that have implemented pre-treatment DPYD testing or have a detailed implementation plan in place were analyzed. Only 33% of sites ordered DPYD testing for all FP-treated patients; at the remaining sites, patients were tested depending on disease characteristics or clinician preference. Almost 50% of sites depend on individual clinicians to remember to order testing without the assistance of electronic alerts or workflow reminders. DPYD testing was most often conducted by commercial laboratories that tested for at least the 4 or 5 DPYD variants considered clinically actionable. Approximately 90% of sites reported receiving results within 10 days of ordering. Conclusion Implementing DPYD testing into routine clinical practice is feasible and requires a coordinated effort among the healthcare team. These results will be used to develop best practices for the clinical adoption of DPYD testing to prevent severe and fatal toxicity in cancer patients receiving FP chemotherapy.

show abstract

Reply to H.S. Hochster

Cited by 3 publications

References 9 publications

Response to the FDA Decision Regarding DPYD Testing Prior to Fluoropyrimidine Chemotherapy

Response to the FDA Decision Regarding DPYD Testing Prior to Fluoropyrimidine Chemotherapy

Strategies for DPYD testing prior to fluoropyrimidine chemotherapy in the US

Strategies for DPYD Testing Prior to Fluoropyrimidine Chemotherapy in the United States

Contact Info

Product

Resources

About