Testing for AR-V7 Gene Variant

Is testing for the AR-V7 gene variant standard practice before treating with Antiandrogens such as Xtandi and / or Zytiga? The logic being that if you test positive, these drugs are a waste of time. 

[Hidden]

Thanks for the background.  It is very helpful.  It strengthens my resolve.  If the doctor wants to put my father on any of these drugs, I will insist on the AR-V7 test.  There is no way I am putting my 95 year old father through any of these drugs given that it has a 35% failure rate without testing.  

[Dan59 in reply to Hidden]

for some of us though, these 2 drugs have worked very good with few if any side effects, 35% failure is better than most odds in advanced cancer meds1

[pjoshea13]

In treatment failure due to AR-V7, any other treatment that, in essence, targets AR but not AR-V7, is going to quickly fail.  But what if there has been no treatment failure yet?

I'm thinking of a situation, say, where Zytiga is started before Lupron has failed.  Perhaps started at the same time as Lupron.  The existence of AR-V7 might not bode well, but it might represent a small percentage of PCa AR at that point.  There might still be advantage to be gained from Zytiga.

Much has been written about AR-V7 in CRPC, but AR-V7 can emerge long before ADT failure.  In fact, AR-V7 isn't always a response to ADT.

In a 2015 study [1]:

- cohort 1 = 100 localized prostate cancer patients   ...   12.0% (12/100)

- cohort 2 = 104 newly diagnosed metastatic PCa patients   ...   21.2% (22/104)

- cohort 3 = 46 CRPC patients   ...   58.7% (27/46)

The percentages shown are for those patients testing positive for AR-V7.  In the case of Cohort 1, prostatectomy tissue was used.  Note that 12.0% for Cohort 1 merely means that 12 men tested positive for AR-V7 expression - it says nothing about the prevalence of AR-V7 in the 12 samples, which was small.

In another study [2], the presence of AR-V7 had no prognostic value with respect to radical prostatectomy failure.  

AR-V7 comes into its own only when treatment starts selecting for it.  At treatment failure, an AR-V7-positive test result presumably implies that the cancer is now AR-V7-dominant.  Useful to know since time & money need not be wasted in treatments likely to offer no benefit.

But if no treatment that targets AR has yet failed, an AR-V7-positive test result says little, other than AR-V7 likely being the cause of failure down the road.  Not enough reason to reject a particular drug until that point is reached.  (The test result will be useful when we have a drug that targets AR-V7.)

IMO

-Patrick

[1]  nature.com/articles/srep07654

[2]  ncbi.nlm.nih.gov/pubmed/230...

[noirhole]

Look for clinical trials for Galeterone they will test for the AR-V7 as part of the trial (free). You maybe able to find a location near where you live.