Genetic tests performed by FoundationOne and Guardant360 come to different conclusions in study of nine cancer patients whose study findings are of interest to pathologists
It’s an understatement to say that tests run by clinical laboratories and pathology groups must be accurate, consistent, and reliable. Thus, research conducted at the University of Washington School of Medicine (UW Medicine) in Seattle, which concluded that genetic tests from two different lab companies produce different results when given to the same patient, is of critical importance.
Oncologists and medical laboratory leaders must have confidence in the results of genetic tests performed on thousands of patients each year. However, according to a UW Medicine statement, a preliminary study comparing two commercially available next-generation genetic sequencing tests in the same cancer patients showed results that could be “markedly” different, depending on the tests performed.
Nine Patients, Two Medical Laboratory Tests, Many Results
While the UW Medicine researchers were seeking ways to improve genetic testing for precision diagnostics and therapeutics, they recognized a need to compare two commercially available genetic-sequencing test offerings:
• FoundationOne; and
• Guardant360.
“Little is known about how next-generation sequencing tests compare when used in the same patients with cancer,” noted the researchers in their study, which was published in JAMA Oncology. “We compared reports from FoundationOne and Guardant360 in nine patients from a community oncology practice to determine the level of concordance between the platforms.”
FoundationOne, by Foundation Medicine, tests solid-tumor cancers to characterize 315 cancer-related genes and 28 other genes often rearranged. The test results highlight genomic alterations relevant to the patient and provide information about targeted therapies and clinical trials for treatment decisions, according to the Foundation Medicine website.
Guardant360, by Guardant Health, employs blood samples to examine the cell-free DNA that dying tumor cells release into the bloodstream of cancer patients. According to a Guardant Health test launch statement, it sequences 73 genes and is the first Pan-Cancer blood test that helps oncologists prescribe the right treatments based on the changing genetics of a patient’s cancer.
Of the nine community-care practice cancer patients that received the FoundationOne and Guardant360 tests, five had breast cancer and four had various other cancers including:
• Pancreatic;
• Lung;
• Salivary gland; and
The study yielded the following results, according to the UW Medicine statement:
• For one patient, neither test found any genetic alterations;
• Eight patients altogether had 45 alterations;
• 10 (22%) of those alterations were found by both tests;
• For two of the eight patients, results between the two reports did not match at all;
• For the eight patients, test reports with identified alterations recommended 36 possible drugs;
• Nine drugs were called out by both tests for the same patients; and
• For five patients, no overlap in suggested drugs was recommended by FoundationOne and Guardant360.
“Our findings indicate that the output from genetic testing can differ markedly depending on which test is applied,” researchers noted.
C. Anthony Blau, MD (above), Professor of Medicine, Division of Hematology, University of Washington School of Medicine, Seattle, was lead researcher for the UW Medicine study that compared genetic tests FoundationOne and Guardant360. (Photo credit: University of Washington.)
These results, however, do not necessarily mean the tests are flawed. In an interview with NPR’s Shots Health News (Shots), C. Anthony Blau, MD, the study’s lead researcher and Professor of Medicine, Division of Hematology, UW School of Medicine, said that certain limitations in each test could be responsible for the varying test results.
Such limitations are described in the Shots article. For example, in a test of tumor tissue, the entire tumor is not biopsied, thereby limiting information about the tumor’s genetics. And blood tests that are used when tumors cannot be sampled also can produce incomplete views of cancer mutations.
“The mutations you are looking for that might guide you to a particular drug can be present in most or only a tiny fraction of cells,” said Blau in the Shots article.
Small Study, Big Impact on Clinical Laboratories
According to Vinay Prasad, MD, Assistant Professor of Medicine at Oregon Health and Sciences University, the UW Medicine study, albeit small in sample size, has a big impact.
“What we are talking about here is precision oncology—the use of sequencing in patients with a range of cancers who have exhausted other options in order to pair them with therapies,” Prasad said in a Medscape Medical News article. “This [high level of concordance] is a prerequisite to the tests being of any clinical use. This paper shows that the majority of the time, the tests give different answers. [It’s] the equivalent of dropping a ton of bricks on this approach,” he concluded.
In their writing, the UW Medicine researchers acknowledged the tests need to be compared with more participants to “improve concordance and clinical utility.”
Genetic Test Developers Comment on UW Medicine Study
In the Shots article, Guardant Health’s Chief Medical Officer Richard Lanman, MD, noted that, “both tests are right,” and that doctors could get more complete results if they ran both tests on everyone. However, he acknowledged, that might be cost prohibitive.
Foundation Medicine’s Chief Medical Officer Vincent Miller, MD, commented in the Shots article that blood tests miss a lot as compared to tests on tumors.
Studies that call attention to a genetic test’s unique variances suggest the need for more research, and should encourage experts to improve the tests toward the goal of precisely targeting and treating cancer. Thus, these are important studies and should command the attention of pathologists and medical laboratory scientists.
There will be more external checking of medical laboratory results. It’s similar to efforts by some researchers who are unable to replicate findings of clinical studies published in peer reviewed journals. So, the UW Medicine study is unique and important for medical lab professionals to review.
—Donna Marie Pocius
Related Information:
Tumor Gene Test Results Can Differ in Same Patients
Comparison of Two Commercially Available Next-Generation Sequencing Platforms in Oncology
Guardant Health Releases Breakthrough Blood Test to Improve Cancer Treatment
‘Ton of Bricks’ Dropped on Popular Cancer Panels?
When Genetic Tests Disagree About Best Option for Cancer Treatment
