Implementing PGx Testing in Oncology: Best Practices, Barriers, and Benefits

In this interview, Houda Hachad, PharmD, vice president, Aranscia, highlights best practices for implementing PGx testing in oncology and what barriers insitutions such as cancer centers and hospitals face in trying to expand this testing.

Please introduce yourself by stating your name, title, organization, and relevant professional experience. 

Hi, I'm Houda Hachad. I'm the vice president of clinical operations here at Aranscia. I'm trained as a pharmacist and a clinical pharmacologist. I spent 20 years in academia and in the industry building drug information technologies around drug interactions and pharmacogenomics (PGx). My goal has always been to advance the safe use of therapeutics for health care providers, but also to empower researchers in the industry to put safer medications on the market. I serve on multiple pharmacogenomic working groups and committees, aiming to standardize and facilitate the adoption of PGx testing. Aranscia is an umbrella company with three entities that are synergistically fulfilling the precision medicine needs of various stakeholders. Our offerings span a wide range of genomic solutions such as diagnostic testing, clinical decision support, workflow optimizations, and facilitating the incorporation of genomic insight in patient care.

What are some best practices for cancer centers and hospitals to go about implementing PGx testing?

Building on the experience that was shared by innovative cancer centers and mostly large academic centers that have implemented DPYD testing to help identify these patients at risk, DPYD started being offered as an optional test. However, multiple centers have started pre-emptive PGx testing for DPYD and helping doctors order this test before the first dose of chemotherapy that includes these medications are provided to the patient. This is the preferable method, and there are multiple ways of doing this.

There are tools for clinical decision support and alerts that can prompt the oncology care team when a diagnosis is made for specific cancers. A treatment protocol for that cancer will include fluorouracil or capecitabine, for example, where we can prompt providers to order the test prior to the initiation of treatment. There are centers that have implemented this approach and have shown a great uptake by their oncologists. In some cases, the centers still ordered the tests maybe a day after the treatment has begun or when toxicities are seen. But this is not the preferable method. It is still possible, but in our case, we promote pre-emptive testing.

Another best practice shared by these centers is their involvement in a multidisciplinary team to ensure proper understanding of genetic results. This includes a pharmacist who acts as the coordinator between the oncologist, the navigators, primary care provider, and the patient’s family to explain the value of the test, the results, and answer questions the oncologists have on specific results. It takes coordination between the pharmacist, oncologist, and laboratory personnel to bring all of this together.

One of the other key components for best practices is the ability to embed the entire DPYD testing workflow within the clinical workflow in the electronic medical record (EMR) for a specific physician so they don’t have to go to multiple places to remember how to order the test, get the results, and act on the information.

What are the barriers to more widespread adoption of PGx testing in oncology?

There are several barriers that can hinder adoption of PGx testing in oncology in general. First, if we go back to the case of DPYD testing, for example, or testing for genes that can inform the prescribing of anticancer medications, there is lack of education or knowledge among the community—including the oncology care team—that these tests are available, that we have tools, have established guidelines, that there are standards, and therefore they are ready for implementation. There is also a lack of internal expertise, going back to the need for a multidisciplinary care team. The care team within these institutions much be educated to promote the use of these tests. We need to have pharmacists with pharmacogenomic expertise who can educate the care team about the what the test is, its value, how the test is done, the turnaround time for the test, and when to test; they have a key role in offering these types of educational sessions.

The second barrier, which is key, is the IT infrastructure or the informatics infrastructure necessary to properly diffuse adoption of the test and use the results promptly. As I said previously, when a dose is administered, institutions that offer this test will have to embed the test results within the electronic health system records that they are using. So, this requires work by informatics to develop these clinical decision supports and integrate them. This is where our company is well positioned because we offer a suite of products that provide a turnkey solution.

Finally, another barrier sometimes is access to a laboratory that has relevant turnaround time.  The result for DPYD needs to be provided to the oncologist as soon as possible and early in the treatment plan, and some laboratories can meet these turnaround time criteria. Finally, the integration of these results by laboratories needs to be achieved within the clinical workflows. Some laboratories have only the ability to give results in a PDF portable document, and sometimes these documents are lost within the EMR. They're not found by the oncologist sooner to act on the information.

There is another barrier that we need to talk about, which is this misperception or concern from oncologists that reducing the dose of these medications early in the treatment could lead to underdosing these patients. And we have now published data that show that dose reduction in these patients with these DPYD variants do not compromise survival among patients, especially in those with metastatic disorders. This is reassuring for oncologists to help promote the use these medications.

Finally, reimbursement is another barrier. Historically, reimbursement has been lagging for some of these tests. However, over the past year especially, although some insurances still labeled the test as not being a medical necessity, in over 90% of the cases when the institution sought reimbursement, it was covered. Medicare, for example, covers for this specific testing when for fluorouracil or capecitabine. This is very encouraging.

Could you describe the benefits of broader PGx testing?

For broader PGx testing—defined as testing a patient pre-emptively or reactively after we know that they're taking certain medications for a number of genes, not just a single gene testing each time—one benefit is that this is a cost-effective approach. With one specific test, we can inform a large number of medications that span multiple specialties. For example, if we leverage the existing guidelines by CPIC that state what the genes are and the medications that are actionable per the result, you can take action. If we leverage these guidelines, we can inform multiple specialties such as pain management, management of cardiovascular disorders, behavioral health cancer, and many more.

With broader testing, we can really focus on targeted patients or populations that are, for example, polymedicated. A cancer patient is an example of a patient who is likely to be taking multiple types of medications, including medications to treat the cancer itself and supportive medications. Or they might be taking medications for pre-existing conditions or comorbidities. When it's time to manage these patients and increase the success of the oncology treatment, it is logical to optimize all their treatment regimens.

Another group of patients who can benefit also from broader PGx testing is the geriatric population. They tend to take multiple medications that are commonly prescribed that can be guided by PGx testing, namely pain medications, antidepressants, cardiovascular medications such as statins, etc. And all of these medications have established actionable guidelines that can help the physician manage or mitigate the risk of adverse events in this vulnerable population.

Broader PGx testing within some implementers has also been shown to benefit populations that are not necessarily polymedicated, such as sick children that are hospitalized who happen to be taking extremely toxic medications, including those with cancer disorders. There is benefit in reducing pain and harm from these medications in these children.