Reply to “A call for reporting of tumor-specific outcomes in studies of DPYD genotyping”

We thank Dr. Tuteja for her letter to the editor on our recent publication: “Real-world implementation of DPYD and UGT1A1 pharmacogenetic testing in a community-based cancer center.”¹ Due to the small sample size in our exploratory analysis, we were unable to report the outcomes by cancer type. As rightly stated by the coauthors, only 6% of the tested patients had breast cancer, none of whom were DPYD variant carriers.

Fluoropyrimidine-based chemotherapy is used to treat various solid cancers, including gastrointestinal and breast cancer, where treatments like capecitabine are used for high-risk or advanced breast cancer cases.² As Dr. Tuteja pointed out, most research on DPYD outcomes focuses on gastrointestinal cancers, where the use of fluoropyrimidines is more prevalent. While DPYD testing is becoming standard in Europe, it still remains limited in the United States, leading to sparse data on outcomes by tumor type.

We advocate for routine DPYD testing before administering fluoropyrimidines due to the demonstrated risk of toxicity in large prospective studies and meta-analyses.^{3, 4} The recent data by Knikman et al.⁵ showed that DPYD-guided dose reductions did not negatively impact cancer outcomes. The case of a breast cancer patient experiencing severe diarrhea from capecitabine in the authors' biobank data highlights the importance of DPYD testing for identifying these high-risk patients. This is especially crucial for debilitated patients for whom fluoropyrimidine may be the second or third line of treatment.

We agree that more data are needed to further assess tumor-specific outcomes. We propose that the solution to reporting such outcomes, as called for by the authors, would be through large collaborative, multi-site data from institutions that have implemented DPYD testing or those with biobanks. These large datasets allow for pooling data and analyzing outcomes separately by cancer type. This type of analysis is underway, and our institution, as well as other researchers, are in the process of collecting such data to evaluate the effectiveness and toxicity outcomes of DPYD-guided dosing. These large outcome-based analyses will further strengthen the evidence for DPYD-based prescribing to increase the adoption of testing.

No funding was received for this work.

The author declared no competing interests for this work.