AR-V7 and Circulating Tumor Cell DNA Testing - Availability and Use

[PhilipSZacarias]

I would like to request an opinion from the experienced and learned members of this forum regarding AR-V7 (androgen receptor variant 7) and circulating tumor DNA (ctDNA) testing.

I was diagnosed with polymetastatic prostate cancer in 2016 (Gleason 9, PSA 29, >5 bone mets). Although my PSA is < 0.1 ng/ml at the present time, I am in the category of patients that will likely progress soon. In order to better decide what my next course of treatment should be, I need to determine whether I have biomarkers that may provide an indication of my response to next the next generation of hormonal therapy (abiraterone or enzalutamide) or chemotherapy (docetaxel or cabazitaxel). I am also considering initiating therapy with the next treatment before castration resistance fully develops (please see evolutionary and game theory posts by fellow members on this forum, highly recommended).

The detection of AR-V7 in the nucleus is associated with a reduced response to abiraterone and enzalutamide and better response to chemotherapy such as docetaxel and cabazitaxel. The detection of aberrant AR, TP53, MYC, BRAF, etc., phenotypes in ctDNA has also been correlated with treatment response. The tests have not been rigorously qualified in clinical trails but there is evidence that many MOs are routinely requesting the tests to “guide” treatment and improve outcomes. Epic Sciences in San Diego does the AR-V7 testing and Guardant 360 in Redwood City, CA does the circulating tumor cell DNA testing. I have contacted both companies and have been informed by Epic Sciences that the service is not available to Canadians and requisitions from Canadian MOs will not be recognized, so the next step is to be referred to a US doctor to obtain access. I have not had a response from Guardant360 yet.

My questions to fellow members are as follows: 1) How many members have requested the AR-V7 and/or ctDNA testing to guide their treatment plan? 2) Has it been difficult to obtain the testing? 3) And finally, does anyone know of an MO in Buffalo who uses the service?

[j-o-h-n]

"experienced and learned members" ... Immediately rules me out.

Good Luck, Good Health and Good Humor.

J-o-h-n Saturday 04/13/2019 6:07 PM DST

[PhilipSZacarias]

Hello John, I did not mean my request to sound exclusionary. I am hoping for a response from members who may have direct experience with the AR-V7 testing. Phil

[Hidden]

My husband and at least one other I'm aware of had the AR-V7 test only after Zytiga started to fail. It was ordered by the MO to see if Xtandi was worth trying without taking the time to wait a month or two to see if psa responded. I think most docs just start Zytiga or Xtandi when Lupron and Casodex fail without checking whether AR-V7 is + or - . Not sure how to get the test without having a doctor order it but I'm also not sure why you would want to. Technology is improving quickly and by the time knowing the answer would be relevant to your treatment, there may be better options. Good luck.

[Sxrxrnr1 in reply to Hidden]

I requested a AR-V7 test after failing both Lupron(immediately), failing Xtandi after some 14 months of very good performance,,,374 to under 10 psa.

Once it failed consider Zytiga but being aware of AR-V7 dilemma that may be cause of failure if preceding drug,,,Xtandi in my case,,,that seceding drug(Zytiga)likely would

fail. In my case I was negative for AR-V7,,, which is good,,,positive is bad.

I recall reading sometime back an article that if every patient being prescribed 2nd Gen AR drugs, were to have a AR-V7 test, that 100’s of millions of dollars that are wasted on patients that are deemed non-respondents to these drugs before they were prescribed them.

The argument being that a thousand dollar AR-V7 test, was very inexpensive compared to a couple or three months on either Xtandi or Zytiga at 10k per month,,,only to find that this patient is a complete non-responder.

Make too much sense to me to ever be considered a SOC strategy.

[Hidden in reply to Sxrxrnr1]

I agree--a simple blood test would be the logical thing to do before prescribing ultra-expensive Zytiga or Xtandi but the test is hardly used. The odds are low one will work following the other, but in my husband's case (on Xtandi since Jan), his psa dropped to the lowest in years (1.3). His psa was <2 on Zytiga but not 1.3.

[Sxrxrnr1 in reply to Hidden]

Very informative, albeit a bit older on initial resistance to 2nd gen AR drugs, why and potentially how to reverse.

Suggests that perhaps 15 percent are resistant from initial use of either. This is why a AR-V7 test might be advisable before any man submits to these drugs. Lessened expense and avoidance of often very bad SE’s for those men who are initially deemed non-responders. Of course will not likely nail them all,,,but perhaps many might benefit.

hematologyandoncology.net/a...

Also a short bit on BAT therapy from John’s Hopkins.

Just added this URL to post.

ncbi.nlm.nih.gov/pubmed/288...

[PhilipSZacarias]

Thank you for the feedback. I am based in Canada and the test is not covered here and therefore I would have pay. Still debating..,