DPYD testing moves further into standard oncology care after guideline updates

New FDA label updates and National Comprehensive Cancer Network (NCCN) recommendations for DPYD testing before fluoropyrimidine treatment are pushing health systems, payers and pharmacists to build workflows aimed at reducing concerning “toxicities” and improving patient safety.

Ahead of the 2026 AMCP Annual Meeting in mid-April, Abby Kim, Pharm.D., senior director of Clinical Strategy and Oncology Specialty Solutions at Prime Therapeutics, and Sneha Sharma, Pharm.D., director of Specialty Clinical Solutions, shared with Managed Healthcare Executive how pharmacogenomics is becoming more integrated into oncology care, especially for fluoropyrimidine therapies such as 5-fluorouracil and the oral Xeloda (capecitabine).

The two presented during the session “Oncology in Focus: What’s Hot, What’s Next!” and highlighted how recent changes in guidance are reshaping clinical workflows and payer expectations.

Fluoropyrimidine therapies are more often used in cancer treatment, but some patients carry dihydropyrimidine dehydrogenase (DPYD) gene variants that affect how they metabolize the drugs. According to the experts, an altered metabolism can increase the risk of severe toxicity and, in some cases, death.

Kim said clinicians and health systems have known about these risks for decades, but adoption of routine testing in the U.S. has lagged behind international efforts. Things then began to change in 2025 following updates to FDA labeling for capecitabine and changes to NCCN recommendations that moved beyond DPYD testing.

According to Cambridge University Hospitals, the DPYD test is a “simple blood test” that checks for the gene changes most likely to cause low levels of the DPD enzyme.

“We recommend doing DPYD testing before you start some of these therapies to lower risks of toxicities,” Kim said. “Payers were probably ahead of the guidelines, and many payers recommended or mandated testing before the use of these drugs. Now we really have all stakeholders coming to the table and saying this is standard of care to recommend testing and perform that testing before patients receive these drugs.”

Kim added that the rapid guideline changes caught some health systems off guard because many organizations had not yet built routine testing workflows. She shared that organizations are now working quickly to coordinate laboratory partnerships, operational processes and coverage considerations.

Sharma told MHE that pharmacists can play a key role in helping providers implement testing and educating care teams about delaying treatment until results are available. She also noted the broader financial and clinical implications tied to avoiding preventable adverse events.

According to Sharma, payer alignment is also improving as more health plans move to formally incorporate DPYD testing into oncology coverage policies.