“Getting a Better Diagnostic (DPYD) into the Standard of Care”

“Getting a Better Diagnostic (DPYD) into the Standard of Care” (Karen Merritt) [#137] Brad Power and Nanthana Ravichandran April 2, 2025 “When the NCCN just updated those guidelines, they said that there's no concrete evidence on how to reduce the dose, which, as an advocate, I disagree with.

I think the CPIC guidelines would be great for dose adjustment, and that's exactly what the institutions that have implemented testing are using.“ - Karen Merritt Meeting Summary As a cancer patient, you may not be aware that you are at risk of being overdosed, under- dosed, and being given drugs that are ineffective, or in tragic cases fatal, which testing could have predicted.

You should get tested to identify your personal risks and to inform your personalized dosing levels before taking certain drugs or getting radiation treatment. In the future, you will be able to measure the effective level of a drug in your body, and then modulate the dose empirically, as opposed to the one-size-fits-all (not personalized) rules for prescriptions.

Consider the story of Karen Merritt, patient advocate and Co-Founder of Advocates for Universal DPD/DPYD Testing , who suffered the heartbreaking loss of her mother—not to colorectal cancer, but to toxicity from an overdose of a chemotherapy meant to treat it.

Her mother could have been tested, but wasn't, for a gene variation (DPYD) which is essential for breaking down and eliminating specific chemotherapies. In most of Europe, testing for this gene variation before administering specific chemotherapies is standard practice. Unfortunately, this is not yet the case in the United States.

In 2022, Karen co-founded the nonprofit organization Advocates for Universal DPD/DPYD Testing to push for change. Their mission is to improve patient safety by making pretreatment DPYD testing a standard of care in the U.S. before being administered certain chemotherapies. They have sent in a proposal to get this testing into the standard care guidelines.

While organizations like the FDA, NCCN, and ASCO have yet to mandate this testing, several leading U.S. cancer centers—such as Dana Farber Cancer Institute, Levine Cancer Institute, and Ochsner —are implementing DPYD testing for better patient safety and outcomes.

Karen's goal is to see this become the norm across the country, ensuring that no more lives are lost due to preventable drug-gene interactions. Why do you need to know about pharmacogenomic testing? Pharmacogenomic testing helps personalize cancer treatment by identifying how your genetic makeup affects your ability to metabolize certain drugs.

In the case of DPYD testing, it can prevent potentially life-threatening toxic reactions to chemotherapy drugs like fluorouracil (also known as 5-Fluorouracil or 5-FU), a chemotherapy medication used to treat various cancers and some skin conditions, and capecitabine, an oral drug that converts into fluorouracil.

ening toxic reactions to chemotherapy drugs like fluorouracil (also known as 5-Fluorouracil or 5-FU), a chemotherapy medication used to treat various cancers and some skin conditions, and capecitabine, an oral drug that converts into fluorouracil.

By understanding your genetic variants, doctors can adjust drug dosages to minimize severe side effects while maintaining treatment effectiveness, ultimately improving patient safety and quality of life during cancer treatment.

“Getting a Better Diagnostic (DPYD) into the Standard of Care” (Karen Merritt) [#137] scheduled to receive chemotherapy treatments using fluorouracil (5-FU) or capecitabine. Testing is a simple blood test or cheek swab. If you have a variant, your oncologist can adjust your dosage to reduce risks.

How can you advocate to improve your access to new tests and personalized dosing in standard protocols?

●Get professional organizations (like NCCN and ASCO) to incorporate the pharmacogenomic tests and procedures in their guidelines (insurance companies typically follow these guidelines) ●Submit citizen petitions to the FDA to revise drug labels and guidelines; support efforts by patient advocacy groups like the American Cancer Society Cancer Action Network to pass biomarker legislation in each state to expand insurance coverage, raise awareness and apply pressure on regulatory bodies ●Highlight patient assistance programs offered by labs (e.

g.

, OneOme provides a $199 test with financial support options for patients who cannot afford the full cost) ●Compile and present patient case studies demonstrating the importance of pharmacogenomic tests; advocate for clinicians, hospitals, and oncology practices to include pharmacogenomic tests as a standard part of initial patient workup, making it easier and more routine; showcase institutions that do incorporate new tests, like the Veterans Administration ●Highlight economic benefits to drug companies, such as reduced adverse events and potential liability ●Collaborate with pharmacogenomics experts to provide scientific evidence supporting routine testing ●Educate yourself about tests for side effects and personalized dosing, share what you learn on support groups and social media, and actively participate in your treatment decisions ●Ask your medical team specific questions about testing and dosing ●Take the time to review and understand consent forms How can you learn more?

●Visit the website of Advocates for Universal DPD/DPYD Testing; advocate for universal DPD testing for cancer patients before starting fluoropyrimidine chemotherapy ●Contact Karen Merritt at karenemerritt@msn.

ore starting fluoropyrimidine chemotherapy ●Contact Karen Merritt at karenemerritt@msn.

“Getting a Better Diagnostic (DPYD) into the Standard of Care” (Karen Merritt) [#137] The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. For the video recording of this conversation, please see here.

“Getting a Better Diagnostic (DPYD) into the Standard of Care” (Karen Merritt) [#137] Meeting Notes KEYWORDS Cancer patient lab, patient advocate, DPYD gene, DPD deficiency, chemotherapy toxicity, pharmacogenomics, FDA guidelines, NCCN guidelines, CPIC guidelines, patient safety, insurance coverage, clinical trials, personalized dosing, patient empowerment, legal action.

SPEAKERS Karen Merritt (67%), Brad Power (10%), Chris Apfel (9%), Roger Royse (5%), Rick Davis (5%), Cindy Ness (3%), Mike Camara (1%), David Plunkett (1%) CHAT CONTRIBUTORS Rick Davis, Bill Paseman, Mike Camara, Dennis Watson, David Plunkett, Chris Apfel SUMMARY Karen Merritt shared her mother's tragic experience with 5-FU chemotherapy, highlighting the lack of DPYD testing that could have prevented severe toxicity and death.

She explained that DPYD deficiency affects 3-6% of the population, with 3% at risk of death, equating to over 1,000 deaths annually in the U.S. Merritt discussed the FDA's recent labeling changes and the NCCN's updated guidelines, emphasizing the need for pre-screening and dose adjustments.

She also mentioned ongoing advocacy efforts, including citizen petitions and legal actions, to improve standard care and patient safety. OUTLINE Introductions and DPYD Gene Explanation ●Karen Merritt, a patient advocate, shared her story and the challenges of getting a new diagnostic into standard care.

●The DPYD gene has a role in breaking down fluorouracil and capecitabine (chemotherapy agents). ●Karen Merritt’s mother was diagnosed with stage three anal cancer in 2014. ●There was a lack of a pharmacogenomics test for DPYD.

karenemerritt@msn.

“Getting a Better Diagnostic (DPYD) into the Standard of Care” (Karen Merritt) [#137] The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action.

You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. For the video recording of this conversation, please see here.

“Getting a Better Diagnostic (DPYD) into the Standard of Care” (Karen Merritt) [#137] Meeting Notes KEYWORDS Cancer patient lab, patient advocate, DPYD gene, DPD deficiency, chemotherapy toxicity, pharmacogenomics, FDA guidelines, NCCN guidelines, CPIC guidelines, patient safety, insurance coverage, clinical trials, personalized dosing, patient empowerment, legal action.

SPEAKERS Karen Merritt (67%), Brad Power (10%), Chris Apfel (9%), Roger Royse (5%), Rick Davis (5%), Cindy Ness (3%), Mike Camara (1%), David Plunkett (1%) CHAT CONTRIBUTORS Rick Davis, Bill Paseman, Mike Camara, Dennis Watson, David Plunkett, Chris Apfel SUMMARY Karen Merritt shared her mother's tragic experience with 5-FU chemotherapy, highlighting the lack of DPYD testing that could have prevented severe toxicity and death.

She explained that DPYD deficiency affects 3-6% of the population, with 3% at risk of death, equating to over 1,000 deaths annually in the U.S. Merritt discussed the FDA's recent labeling changes and the NCCN's updated guidelines, emphasizing the need for pre-screening and dose adjustments.

She also mentioned ongoing advocacy efforts, including citizen petitions and legal actions, to improve standard care and patient safety. OUTLINE Introductions and DPYD Gene Explanation ●Karen Merritt, a patient advocate, shared her story and the challenges of getting a new diagnostic into standard care.

●The DPYD gene has a role in breaking down fluorouracil and capecitabine (chemotherapy agents). ●Karen Merritt’s mother was diagnosed with stage three anal cancer in 2014. ●There was a lack of a pharmacogenomics test for DPYD. ●Her mother had severe toxicity reactions and died. ●There is a lack of informed consent about DPD deficiency.

luorouracil and capecitabine (chemotherapy agents). ●Karen Merritt’s mother was diagnosed with stage three anal cancer in 2014. ●There was a lack of a pharmacogenomics test for DPYD. ●Her mother had severe toxicity reactions and died. ●There is a lack of informed consent about DPD deficiency.

Challenges and Advocacy Efforts ●Karen Merritt discussed the high risk of severe toxicity and death due to DPD deficiency. ●The supposed antidote, VistoGuard, has a high cost, short time window and prior authorization requirements. ●Pre-screening for DPD deficiency and dose adjustment are based on CPIC guidelines.

●The mission of her nonprofit is to improve the standard of care for cancer patients undergoing 5-FU and capecitabine chemotherapy.

“Getting a Better Diagnostic (DPYD) into the Standard of Care” (Karen Merritt) [#137] Legislative and Clinical Efforts ●Karen Merritt discussed the citizen petitions to the FDA to revise drug labels and the changes in labeling for capecitabine and 5-FU. ●The FDA-AACR's DPD workshop led to the issuance of an FDA safety announcement in January 2025.

●Changing NCCN and ASCO guidelines is challenging. There has been progress in Europe. ●A recent update in NCCN guidelines says to consider DPYD genetic variants prior to therapy. Insurance and Patient Empowerment ●Karen Merritt emphasized the importance of insurance coverage for DPYD testing and the role of NCCN guidelines. ●Fight CRC's care sequences call out DPYD testing.

●Institutions need to make DPYD testing easy for providers. ●Patient empowerment is needed and informed consent. Personalized Dosing ●Chris Apfel and other participants discuss the scientific evidence for dose adjustments and the need for personalized dosing. ●Roger Royse and other participants discuss the broader issues of patient empowerment, standard of care, and the role of FDA guidance.

“Getting a Better Diagnostic (DPYD) into the Standard of Care” (Karen Merritt) [#137] TRANSCRIPT Brad Power This is the Cancer Patient Lab. Welcome to our weekly webinar series. Today, we're honored to have with us Karen Merritt, a patient advocate who will be sharing her story.

She was a caregiver for a loved one who experienced an unfortunate toxicity that could have been caught with diagnostic testing. She will tell us about that story as well as the challenges of getting a new diagnostic test into the standard of care. Before we get started, I will make a disclaimer. This webinar is only informational, and is not medical advice.

Our aim is to provide patients and caregivers with information they can take to their medical team to help improve their care. We are a 501(c)(3) nonprofit and welcome donations from anyone inspired by the services we provide to patients and caregivers. Karen Merritt 1:26 Thank you so much for having me.

It's so nice to see cancer survivors, and all those fighting to get a better diagnostic into the standard of care.