Commercially available liquid biopsy data may be misleading


A newly published research letter in JAMA Oncology is entitled “Patient-paired sample congruence between 2 commercial liquid biopsy tests”. The two tests are both said — by the companies that market them — to have high clinical sensitivity and specificity in the identification of specific genetic markers associated with high-risk forms of prostate cancer.

The authors of this new research letter (Drs. Torga and Pienta from the Johns Hopkins University School of Medicine) are clearly far more tactful than your sitemaster, who might have entitled the original research letter as, “Utter lack of any patient-paired sample congruence between 2 commercial liquid biopsy tests.”

Basically, Torga and Pienta wanted to know which of two commercially available liquid biopsy tests was the better one for Johns Hopkins to consider using in the diagnosis of patients with metastatic prostate cancer. What they discovered (after sending exactly the same blood samples from 40 patients to the two different CLIA-certified laboratories) is distinctly disturbing. For a relatively non-scientific commentary on this study, see this article on the ScienceDaily web site.

These tests are supposed to be able to help clinicians determine what “the best” type of drug therapy may be for treatment of — primarily — men with metastatic, castration-resistant prostate cancer. For example, do they have genetic mutations suggesting that treatment with a PARP inhibitor or some other drug might be a particularly good idea?

The companies marketing the two different liquid biopsy tests used in this study differ in which genes, and regions within each gene, are covered. This is to be expected. However, 25/40 patients in this study (63 percent) were known to have at least one genetic mutation reported within the overlapping genetic sequences covered by both companies.

Now remember that the two companies were both sent exactly the same blood samples on which to run their tests. In other words, blood samples were drawn from each of 40 patients. Part of each blood sample was sent to one company and another part of the same blood sample was sent to the other company. So the companies were running their tests on identical blood specimens.

What did the authors find?

  • The results provided by the two companies rarely matched each other.
  • When the authors compared the results from overlapping genetic sequences supposedly identifiable by each of the two tests, the results from both companies matched for all mutations reported in only 3/40 patients (7.5 percent of cases).
  • In 6/40 patients (15 percent), both companies’ results matched for at least one of the reported mutations.
  • In 16/40 patients (40 percent), no mutations that were potentially covered by both test panels were reported by either company.

In what has to be one of the kinder pieces of criticism one might want to make, Dr. Torga is reported to have stated that:

Liquid biopsy is a promising technology, with an exceptional potential to impact our ability to treat patients, but it is a new technology that may need more time and experience to improve. We can’t tell from these studies which laboratory’s panel is better, but we can say that certification for these laboratories must improve.

The “New” Prostate Cancer InfoLink has a rather different take on the results from this study, as follows:

  • Current commercially available liquid biopsies designed to conduct genetic testing of cDNA as a guide to the selection of drug therapy for men with advanced prostate cancer are simply not yet ready for prime time.
  • The role of this type of liquid biopsy to test patients with other forms of advanced cancer as a means to select “personalized” drug therapy may well also need to be reevaluated on the basis of the findings of this study.

We would note, however, that when specific genetic tests have been evaluated and approved by the FDA as “companion diagnostics” for use to test for specific mutations that are indicative of the value of treatment with a specific drug therapy, the situation is very different. Those companion diagnostic tests appear to have a highly repeatable level of specificity and selectivity and can be relied on to do what they are intended to do.

If you want to know exactly which commercially available liquid biopsy tests were being used in this study, click here and scroll down to look at the “First Page Preview”.

2 Responses

  1. I would have been more interested to see how Guardant compares with Foundation Act … anecdotally these are the two most common commercial liquid biopsy tests I have seen used. I have never encountered PlasmaSELECT.

  2. Dear Rick:

    At the time this study was done, it would not have been possible to use the Foundation One test because it wasn’t commercially approved. The Guardant and the PlamaSELECT tests were (because they are CLIA approved). That is a major point of this trial … that CLIA approval doesn’t necessarily provide sufficient evidence of the clinical utility of a genetic test.

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