FDA-AACR Workshop
To Test or Not to Test – That Is the Question: DPD Deficiency and Weighing Potential Harms
Date: January 16, 2025 | 9 a.m.–3 p.m. ET
Location: The Bethesda Marriott, 5151 Pooks Hill Rd, Bethesda, MD 20814
registration
agenda outline
OVERVIEW
The U.S. Food and Drug Administration (FDA) Oncology Center of Excellence and the American Association for Cancer Research (AACR) are collaborating on a one-day hybrid public workshop to explore the considerations for dihydropyrimidine dehydrogenase (DPD) deficiency testing before chemotherapy with fluoropyrimidines.
Fluoropyrimidine drugs, including 5-Fluorouracil (5-FU) and capecitabine (Xeloda), are frequently used to treat various solid tumors and remain the backbone of many combination therapies. The DPD enzyme plays a vital role in the breakdown of these drugs into non-toxic products, and individuals with certain genetic variants in the DPYD gene may have complete or partial DPD deficiency, which can lead to an increased risk of severe adverse reactions. As a result, more standardized approaches to testing for DPD deficiency could improve patient safety. In 2022, the FDA product labeling for Xeloda (capecitabine) was updated to include new information on DPD deficiency, and 5-FU product labeling was similarly updated in 2024. In conjunction with the 2022 labeling revisions for Xeloda, FDA also issued its response to a Citizen’s Petition requesting labeling revisions recommending pre-treatment testing be considered to identify patients with DPD deficiency.
The purpose of this workshop is to provide an interdisciplinary forum to examine the existing information and evidence surrounding DPD deficiency testing, consider the potential clinical implications of requiring testing, including potential unintended consequences, and to discuss the regulatory considerations for modifying FDA product labeling to require testing.
WORKSHOP CO-CHAIRS
Patricia M. LoRusso, DO, PhD (hc), FAACR, President, the American Association for Cancer Research
Jennifer Gao, MD, Associate Director for Education, Oncology Center of Excellence, U.S. Food & Drug Administration
agenda outline
| Time | Sessions and Topics |
| 9-9:10 a.m. | Welcome and Opening Remarks |
| 9:10-9:40 a.m. | Fireside Chat |
| 9:40-9:50 a.m. | Break |
| 9:50-11 a.m. | Session 1: Current Landscape – DPD Testing and FDA Product Labeling |
| Topics: | |
| Evidence for complete deficiency | |
| Currently available tests | |
| Knowledge gaps and management of partial deficiency | |
| Race/ethnic considerations with variants | |
| Testing approaches – including genotype-phenotype concordance, turnaround, etc. | |
| 11-11:10 a.m. | Break |
| 11:10 a.m.-12:30 p.m. | Session 2: Current Landscape – Clinical Practice |
| Topics: | |
| Current clinical practice and treatment contexts amenable to testing | |
| How clinicians currently interpret DPD testing reports – especially if variants reported are not well characterized or heterozygous | |
| 12:30-1:15 p.m. | Lunch |
| 1:15-2:30 p.m. | Session 3: Future Direction – Where Do We Go From Here? |
| Topics: | |
| Anticipated impacts of requiring pre-treatment DPD deficiency testing based on 5FU/Capecitabine drug utilization | |
| Implications for clinical practice if testing is required – including 1st line treatment vs 2nd line treatment and beyond | |
| Are available tests reliable enough for testing to be required at this time? | |
| Are better clinical recommendations on testing methodologies needed before requiring testing? | |
| 2:30-2:45 p.m. | Patient Perspective |
| 2:45-3:00 p.m. | Closing Remarks |
