NEW YORK – The American Cancer Society's Cancer Action Network (ACS CAN) on Thursday released consensus recommendations for how the US healthcare system can implement pharmacogenomics testing in cancer care with an eye toward equity and overcoming adoption barriers.
"We are behind in implementing PGx testing as a routine part of care," Kirsten Sloan, ACS CAN's managing director of public policy, said at a meeting of cancer experts and patient advocates in Washington, D.C., where the advocacy group released the recommendations. "In many cases, where PGx testing has made its way into care, it has often been inequitable."
The report, developed by a PGx working group convened by ACS CAN over the past year, touches on a wide range of topics, from the discovery of PGx variants to their clinical implementation, and puts forth recommendations for the US Food and Drug Administration, guidelines bodies, payors, and other stakeholders.
ACS CAN urges sponsors to include diverse ancestral populations in clinical trials and incorporate pharmacogenes where evidence suggests they may impact treatment response; combine PGx data within existing treatment and outcomes databases; improve data collection on treatment-related adverse events; revamp how PGx information is relayed and kept up to date on drug labels; improve PGx test coverage, decision support within electronic medical records, and clinicians' knowledge; and create incentives for conducting PGx testing.
In a keynote presentation at the meeting hosted by ACS CAN on Thursday, Karen Merritt, a patient advocate and founding member of Advocates for Universal DPD/DPYD Testing, shared the story of the severe toxicity her mother suffered after being administered 5-FU, a chemotherapy that's been linked with life-threatening adverse reactions in patients with certain DPYD PGx alterations that lead to dihydropyrimidine dehydrogenase deficiency. Merritt, who said she believes the adverse reaction caused her mother's death, and other patients and relatives of those who have suffered similar toxicities are pushing for preemptive DPYD testing to become standard care for cancer patients prescribed the fluoropyrimidine-based chemotherapies 5-FU and Xeloda (capecitabine).
Currently, the National Comprehensive Cancer Network doesn't recommend DPYD testing before prescribing these chemotherapies. The FDA recently updated Xeloda's label to further clarify that patients with certain pharmacogenetic variants are at increased risk for life-threatening adverse reactions, but stopped short of recommending routine PGx testing.
Absent backing for testing from the NCCN or FDA, cancer centers haven't widely adopted DPYD testing in cancer care and testing companies haven't standardized test performance. As part of her story, Merritt stressed how lack of standards for what DPYD testing entails creates challenges for patients. After her mother died, the family sent out a blood sample to test for DPD deficiency, and it turned up negative. However, she later learned that the commercial lab that conducted the analysis only tested for one common variant.
Merritt, who was later tested at a lab that tests for eight DPYD variants, discovered that she has a rare mutation that was likely inherited from her mother. "It's bad enough to lose a loved one to cancer," she said. "It's devastating losing them to the drug that was supposed to cure that cancer."
ACS CAN in its report said PGx tests used in specific prescribing situations should include all clinically relevant variants and should be updated with additional variants as they're discovered. Developers of PGx tests should further pay attention to variants that are relevant to non-European ancestral groups, which have been historically underrepresented in research.
If a test includes variants for which evidence of clinical relevance is uncertain, that should be clearly noted, according to the report.
Before sending a patient's blood sample out to an outside lab for DPYD testing, it's critical to understand what variants they're testing for, said Jai Patel, chair of the department of cancer pharmacology and pharmacogenomics at Atrium Health's Levine Cancer Institute in Charlotte, North Carolina.
"When that result comes back in, there is a chance that it could be a false-negative result," he said. Patel, who recently coauthored a paper on the implementation of an in-house DPYD testing program, said the industry needs to set standard DPYD genetic variants that should be tested for and ensure variants common in racial and ethnic minority populations aren't overlooked.
He added that insurance coverage of PGx testing is necessary for adoption. Today, such coverage in oncology is low and inconsistent across payors. "A provider's very unlikely to order a multi-gene test, or maybe even single-gene test, if that patient is going to have out-of-pocket costs," Patel said. "That patient's insurance is dictating whether or not that patient's going to receive testing."
ACS CAN also recommends setting policies that ensure coverage for tests specified in labels of FDA-approved drugs and nationally recognized clinical practice guidelines.
ACS CAN's recommendations have been endorsed by a dozen personalized medicine and cancer organizations, including the Association of Community Cancer Centers, the Personalized Medicine Coalition, and the American Society of Pharmacovigilance.