Pharmacogenomics Testing in Oncology

Pharmacogenomics (PGx), the study of how genes affect a person’s response to drugs, continues to emerge as a critical tool for personalized medicine. By identifying the genetic factors that influence drug metabolism and response, healthcare providers can tailor treatments to individual patients, potentially improving therapeutic outcomes, reducing adverse drug events (ADEs), and enhancing a range of other quality measures for healthcare organizations.

How is pharmacogenomics testing utilized in oncology to enhance chemotherapy efficacy, reduce adverse drug events and accelerate appropriate treatment?

Pharmacogenomic testing holds promise in the field of oncology, as PGx enables personalized chemotherapy treatment plans, which can maximize drug efficacy and reduce ADEs. PGx testing can also accelerate the timeline for the administration of the most appropriate cancer treatments.

PGx testing can maximize chemotherapy drug efficacy. Pharmacogenomic testing allows oncologists to tailor cancer therapies to an individual’s genetic makeup, which can increase the efficacy of the treatment. In other words, when clinicians understand a cancer patient’s genes, they can select the chemotherapy drugs and dosage that are likely to be the most effective.
PGx testing can reduce adverse reactions to chemotherapy drugs. Many cancer patients who receive chemotherapy experience ADEs.[1] The severity of adverse reactions can be highly individualized and are often the result of differences in how chemotherapy drugs are metabolized. Pharmacogenomic testing can be used to identify genetic inherited variants mutations that impact drug metabolism, providing meaningful data for dose adjustments or alternative treatments to improve tolerance and adherence. In addition, PGx testing can also reveal potential interactions with other medications the patient is taking, allowing for better management of polypharmacy.
PGx testing can accelerate time to appropriate cancer treatments. Oncologists need to get their patients the right medications as soon as possible. Pharmacogenomic testing reduces trial-and-error prescribing and shortens the time to appropriate, informed, and targeted treatment.

What is the role and impact of DPYD genotyping in fluoropyrimidine-based chemotherapy for oncology patients?

One well-characterized example of pharmacogenomics in oncology is the use of DPYD genotyping prior to the administration of fluoropyrimidine-based chemotherapy. DPYD is a gene that encodes dihydropyrimidine dehydrogenase (DPD), an enzyme essential for metabolizing fluoropyrimidines such as 5-fluorouracil (5-FU) and capecitabine that are used in some chemotherapy regimens. Inherited variants in the DPYD gene can reduce or even negate DPD enzyme activity, potentially leading to severe side effects from treatment-related toxicity.

Researchers estimate that approximately 5% of the population has an absolute or partial deficiency of the DPD enzyme. [2] In April 2020, the European Medicines Agency (EMA) recommended testing for DPD deficiency prior to starting fluoropyrimidine treatment [3] and now, using PGx testing to identify DPYD inherited variantsis widely accepted as the standard of care across Europe for reducing ADEs from fluoropyrimidine-based chemotherapy, without adversely affecting outcomes. [4] Clinicians, pharmacists, and other advocates in the United States continue to call on the FDA to follow suit and recommend preemptive DPYD testing and genotype-based dose adjustment for cancer patients receiving fluoropyrimidine-based treatments. [5]

“I and others have done a lot of work pulling together the data, working with patient advocates and others to draw attention to this matter, and we’re seeing a lot of momentum,” says Daniel L. Hertz, PharmD, PhD, Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan. As Dr. Hertz points out, the National Comprehensive Cancer Network (NCCN) recently issued updated clinical guidelines that embrace DPYD genotyping as a tool for tailoring fluoropyrimidine chemotherapy for colon, rectal, anal, and small bowel cancers. [6,7]

Moreover, the clinical utility of PGx is being investigated across other use cases, he adds. For instance, in 2023, researchers in Europe found that using a 12-gene pharmacogenetic panel to guide drug prescribing significantly reduced the incidence of clinically relevant ADEs. [8]

What are the anticipated benefits and future implications of PGx testing in oncology?

As researchers refine our understanding of drug–gene relationships and pharmacogenomics continues to prove its clinical utility, we anticipate that PGx testing will be increasingly adopted into oncology clinical practice. PGx testing provides meaningful data that can be used to personalize treatment, enhance the efficacy of chemotherapy drugs, and prevent severe adverse drug events. These benefits suggest that successful implementation and integration of PGx testing can help pave the way toward improved patient outcomes and a more cost-effective, efficient healthcare system.

Learn more about pharmacogenomics testing at thermofisher.com/pgxeducation .

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