Unmasking Hidden Risks:

DPYD Deficiency and Chemotherapy Toxicity

Approximately 3–5% of the population carries a DPYD gene variant leading to partial DPD deficiency, significantly increasing their risk of severe or fatal toxicity when treated with 5-FU or capecitabine chemotherapy.

The Current Clinical Challenge

for Physicians Prescribing 5-FU/capecitabine chemotherapy

Standard chemotherapy dosing doesn’t account for genetic differences in drug metabolism. Patients with DPD deficiency are unable to effectively break down 5-FU or capecitabine, leading to drug accumulation and heightened toxicity risks. Without pre-treatment screening, these patients remain unidentified until adverse reactions occur, which can be life-threatening.

Mira Precision ToxNav® Solution

  • Non-Invasive Testing: Utilizes a simple buccal (cheek) swab for DNA collection.
  • Rapid Turnaround: Delivers results within 48–72 hours, facilitating timely treatment decisions.
  • Personalized Care: Identifies patients at risk, allowing clinicians to tailor chemotherapy dosing or consider alternative therapies, thereby enhancing patient safety and treatment efficacy.
Clinically validated and economically impactful, Mira Precision ToxNav® identifies patients at significant risk of severe toxicity from 5-FU and capecitabine chemotherapy. Supported by robust peer-reviewed evidence, ToxNav® empowers personalized treatment decisions, reduces healthcare costs, and significantly improves patient outcomes and quality of life.
“ We developed our ToxNav test to identify cancer patients that have a high likelihood of undergoing extreme toxicity to 5FU/capecitabine treatment, which is one of the most widely used cancer drugs in the world. We have already clinically proven that ToxNav identifies patients susceptible to extreme toxicity and are excited to have partnered the test with Mira Precision, who have complementary expertise to advance ToxNav in the USA. We look forward to a long and productive relationship with Mira Precision as we advance ToxNav to widen its clinical utility in the USA and save more patient lives. ”

Dr. David Kerr, Founder and Director of the Board of OCB, Professor of Cancer Medicine, Oxford University

Clinical and Economic Impact Backed by Peer-Reviewed Evidence:

  1. Clinical Efficacy Proven:
    ToxNav® accurately identifies patients at highest risk of severe (grade 4–5) fluoropyrimidine-related toxicity, as demonstrated in the large-scale FUSAFE meta-analysis of DPYD gene variants (Le Teuff et al., 2024).
  2. Healthcare Cost Reduction:
    DPYD testing prior to chemotherapy significantly reduces costly toxicity-related hospitalizations. Economic modeling in the UK shows that extended DPYD testing is cost-effective in metastatic breast cancer (Koleva-Kolarova et al., 2023a).
  3. Improved Patient Outcomes:
    A prospective real-world utility study (PRECISE) demonstrated ToxNav®, paired with toxicity monitoring, improves treatment safety and enhances clinical decision-making (Lee et al., 2019).
  4. Value-Based Care Alignment:
    Budget impact analyses across multiple countries confirm that implementing DPYD testing supports sustainable oncology care by preventing adverse events and aligning with value-based healthcare priorities (Koleva-Kolarova et al., 2023b).
  5. Enhanced Treatment Adherence:
    Comprehensive panels that include both DPYD and ENOSF1 variants (as in ToxNav®) outperform single-gene approaches in predicting capecitabine-related toxicity (Palles et al., 2021).

References

  • Koleva-Kolarova, R., Vellekoop, H., Huygens, S., Versteegh, M., Rutten-van Mölken, M., Szilberhorn, L., … Tsiachristas, A. (2023a). Cost-effectiveness of extended DPYD testing before fluoropyrimidine chemotherapy in metastatic breast cancer in the UK. Personalized Medicine, 20(4), 339–355. https://doi.org/10.2217/pme-2022-0099
  • Koleva-Kolarova, R., Vellekoop, H., Huygens, S., Versteegh, M., Rutten-van Mölken, M., Szilberhorn, L., … Tsiachristas, A. (2023b). Budget impact and transferability of cost-effectiveness of DPYD testing in metastatic breast cancer in three health systems. Personalized Medicine, 20(4), 357–374. https://doi.org/10.2217/pme-2022-0133
  • Le Teuff, G., Cozic, N., Boyer, J.C., Boige, V., Diasio, R.B., Taieb, J., … Etienne-Grimaldi, M.C. (2024). Dihydropyrimidine dehydrogenase gene variants for predicting grade 4-5 fluoropyrimidine-induced toxicity: FUSAFE individual patient data meta-analysis. British Journal of Cancer, 130, 808–818. https://doi.org/10.1038/s41416-023-02517-2
  • Lee, L.Y.W., Starkey, T., Sivakumar, S., Fotheringham, S., Mozolowski, G., Shearwood, V., … Kerr, D. (2019). ToxNav germline genetic testing and PROMinet digital mobile application toxicity monitoring: Results of a prospective single-center clinical utility study—PRECISE study. Cancer Medicine, 8, 6305–6314. https://doi.org/10.1002/cam4.2529
  • Palles, C., Fotheringham, S., Chegwidden, L., Lucas, M., Kerr, R., Mozolowski, G., … Kerr, D. (2021). An evaluation of the diagnostic accuracy of a panel of variants in DPYD and a single variant in ENOSF1 for predicting common capecitabine related toxicities. Cancers, 13, 1497. https://doi.org/10.3390/cancers13071497

Learn More About Mira Precision ToxNav®

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