New test now available for identification of AR-V7 mutations in mCRPC

According to a media release issued yesterday, Genomic Health has now made available a commercial test for risk of the AR-V7 mutation in men with metastatic, castration-resistant prostate cancer (mCRPC). The full text of this media release can be read on the Genomic Health web site.

The so-called Oncotype DX® AR-V7 Nucleus Detect™ test is the test initially developed by Epic Sciences. It can accurately detect the presence of a splice variant of the androgen receptor protein (the AR-V7 variant) in the nucleus of circulating tumor cells (CTCs).

The value of knowing the AR-V7 status of a specific patient is that can assist clinicians in knowing whether men treated with an androgen receptor-signaling inhibitor, such as enzalutamide or abiraterone acetate (and perhaps also apalutamide, although that is still to be determined), need to consider treatment with a different form of androgen receptor-signaling agent or whether they need to be switched to treatment with chemotherapy.

3 Responses

  1. This test has long been expected … at the last PCRI meeting we were told to expect availability in 1Q 2018.

    Subsequently, Chuck Ryan told me that many researchers no longer believe the positive AR-V7 variant is a key factor in failing abiraterone and enzalutamide. My understanding is that apalutamide is not AR-V7 sensitive — that is supposedly one of its advantages over abiraterone and enzalutamide. I cannot elaborate on Ryan’s comment — if others can, I would be most grateful.

    Based on anecdotal reports, many doctors prefer to try abiraterone or enzalutamide rather than testing for AR V7 — but they are not having to pay for the drugs! It should be noted that Johns Hopkins has had a commercial test available for almost 2 years that runs around $1,000 and has complicated logistics to use it. Over this period many of our virtual group participants have requested the test, and their doctors have declined suggesting that if the patient fails abiraterone/enzalutamide they will just move on to the next therapy.

    Beyond the time factor of how long it takes to fail, the test largely boils down to a financial play — is it cheaper to run the test versus paying the very high monthly copay for abi/enz until it fails?

    This announcement does not include mention of the test’s price, but the Johns Hopkins test at $1,000 is a lesser outlay than the co-pay for most men — and insurance appears to be picking it up.

    My guess is that Genomic Health already has a market for its new test with the insurance companies, who will insist on testing before approving abiraterone/enzalutamide. I would not be at all surprised if we now see a flurry of articles on why the AR-V7 variant is less significant than previously thought.

  2. Dear Rick:

    If I am interpreting the media release correctly, what Genomic Health is saying is only that if the patient seems to be progressing on enzalutamide or abiraterone, this test can help to determine whether it is because the patient is AR-V7 positive (in which case there would be little point in switching the patient to the other of the two).

    I can see the argument for testing for the AR-V7 mutation prior to treatment with enzalutamide or with abiraterone acetate. If the payors wish to request such testing, that’s not unreasonable so long as the testing laboratories can meet the demand. Whether it is meaningful to conduct such testing prior to giving the patient abiraterone or enzalutamide is a rather different question.

    I have seen no data demonstrating that: (a) a patient on apalutamide is at no risk for induction of the AR-V7 mutation, or (b) a patient who is progressing on apalutamide could not be doing so because they had an AR-V7 mutation.

    The question of the real clinical significance of the AR-V7 mutation in the overall management of advanced forms of prostate cancer appears to me to be up for debate for the simple reason that most men with mCRPC can be shown to have multiple, sometimes serial mutations. It may be critically important to know which ones occurred when — and we rarely know that at the present time.

  3. Tx for the clarification, Mike – makes sense!

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