AR-V7 testing should be done before Xtandi?

[Daddysdaughter]

My father will begin using Xtandi. Should he have this test done prior to starting?

[YostConner]

The test helps predict the effectiveness of Xtandi. I've just finished 32 months on Zytiga. My MedOnc would like to try Xtandi. He ordered the AR-V7 blood test.

[Hidden]

Personally, I would try Xtandi and see if it works rather than relying on the test to tell me.

Here is an article written earlier this year.

ascopubs.org/doi/full/10.12...

Here's a quote from the article.

"In men who have not been exposed to either abiraterone or enzalutamide, it is less common to have AR-V7–positive CTCs. Moreover, these may be less predictive of a poorer response because 4 of 15 of these men did respond to abiraterone or enzalutamide in the current study. Therefore, in most cases, it is unlikely that the presence or absence of AR-V7–positive CTCs would play a major role in therapeutic decisions in this patient population. On the basis of these considerations, in the short term, it seems likely that assessment of AR-V7 will continue to be carried out primarily in the context of clinical trials. However, as more therapeutic options become available, these or related assays may play an increasingly important role in the clinic."

[BigRich in reply to Hidden]

Thank you for a very informative article. I still am going to have the AR-V7 test; so that, I will know if I take Zytiga in addition to Lupron or I seek another additional treatment.

Rich

[Daddysdaughter in reply to BigRich]

Did you have he test done?

[BigRich in reply to Daddysdaughter]

There where not enough cancer cells in my blood draw to do the test. Rich

[pjoshea13]

AR-V7 preponderance is one of a number of reasons for resistance to therapies that ultimately target the androgen receptor [AR]. However, lesser numbers of AR-V7 positive PCa cells can exist at any stage.

The test is perhaps worthwhile after failing Zytiga, before starting Xtandi - & vice versa - but I wouldn't bother otherwise.

"The androgen receptor splice variant AR-V7 has recently been discussed as a predictive biomarker for nonresponse to next-generation androgen deprivation therapy (ADT) in patients with castration-resistant prostate cancer. However, we recently identified one patient showing a response from abiraterone despite expression of AR-V7 in his circulating tumour cells (CTC)." [1]

Further: "... we precisely assessed the response in a cohort of 21 AR-V7 positive castration-resistant prostate cancer patients who had received therapy with abiraterone or enzalutamide. We detected a subgroup of six AR-V7 positive patients showing benefit from either abiraterone or enzalutamide."

In other words, being AR-V7-positive is not enough. We need to know whether AR-V7 is the cause of prior failure.

Can anyone tell me: is the AR-V7 test Yes/No? Or does it return a % of affected circulating cells?

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/274...

[Hidden in reply to pjoshea13]

You said: "The test is perhaps worthwhile after failing Zytiga, before starting Xtandi - & vice versa - but I wouldn't bother otherwise."

I agree with that approach. If either doesn't work, at that point you'd want to know why. You'd want to know what mutations were there and if you could possibly find a targeted treatment for whatever mutations were found.

As far as I know, the tests do indicate the % of cells that are AR-V7. In another article I read, they concluded that >5% of CTCs need to be AR-V7 before it's considered to have an effect.

There is also the possibility of the development of neuroendocrine features. That can also be the reason for resistance since they are not AR dependent. To determine if that's the case, I think you need to do a biopsy and the cells need to examined under a microscope.

[Dan59 in reply to Hidden]

Pretty sure you can determine small cell with a CGA, CEA ,or several other blood test from a lab.

[BigRich]

`Thank you for the information.

Rich

[TRinVirginiaBeach]

Once we determined my PCa had become resistant to Firmagon solo, we decided to add Xtandi. We considered the genetic testing, but, my MO said that by the time we got insurance approval and then got the genetics results, we would know if the Xtandi was working.

Luckily for me, my PSA began dropping immediately and was <.01 within 60 days of adding Xtandi.

[wifeofvet]

i'm not well versed in ARV7, not truly understanding it, but I know that after re-testing my husband's biopsy for both ARV7 and PARP, he was negative for brca 1 and 2, and his doctors warned he might not respond well to enzalutamide (i am ''presuming'' from the ARV7 results after reading about it on this site). He still got three years from enzalutamide...but, it is now failing him. That's all i've got on (maybe) ARV7. During this time he also got docetaxel and it failed him completely. They switched to a platinum based chemo (name escapes me) and he failed that, also...NOT ONE LITTLE DROP OF PSA from either.

12+ years in, gleason 10 at diagnosis with a little note to his urologist from the urologist's pathologist pal at Bethesda that said, ''if there were a gleason 11 or 12, this would be your guy''), immediate Lupron and Casodex, three months later, 42 IMRT treatments, Casodex for 5 years. Three months off Casodex after it failed before Zytiga was approved, PSA soared to 999. Zytiga came out, he got 4 years from Zytiga, PSA then again on the rise after 4 years to 220, chemotherapy, then enzalutamide. He remained on Lupron throughout the 12 years, along with IV Zometa, monthly (beginning in year three).

He crested 12-year survival at the end of july '17 while beginning to fail enzalutamide. Along the way, once during his Zytiga days, they spot radiated bone mets in his shoulder (12 IMRT) and recently, while on enzalutamide, they spot radiated bone mets in his femur (3 treatments) and right knee (3) and, again, in his right calf (1). He is currently awaiting Zofigo as his PSA has climbed to 900 again on enzalutamide while we wait to hear from Bayer on is ''RIGHT TO USE'' request for darolutamide, which is showing some benefit over both Zytiga AND Xtandi.

In his case, having been exposed to large amounts of Agent Orange at age 20 for two years in Vietnam, he also developed squamous cell carcinoma of the larynx mid-stint on Zytiga and had 33 IMRT to the throat and a flap laryngectomy that failed to get all of the cancer as it had already spread to his nodes and thyroid wall. He underwent a node resection a year later. His prognosis was dire on the throat cancer, 5-year survival was expected to be less than 3% after it returned immediately following the surgery. THAT was 6 years ago, and since then both Opdivo and Keytruda hit the market. He received Optivo for almost a year and is doing even better on Keytruda for the last three months, neither of which affected his PSA in any way...so, no prostate cancer advantage from either. I add this only to say that during the surgery period, he had to cease taking the Zytiga for over 30 days TWICE, because of the prednisone and possible bleeding complications during surgery from the prednisone. His PSA during this time went up 13 points and 20 points during each surgery period, but went back down after resuming Zytiga.

During his entire stint with both cancers, treated by the VA hospital system, we had multiple oncologists. His prognosis at biopsy was 1% chance of surviving three years from the prostate cancer (translation: about 18 months). His Baylor educated urologist and one ''old-timer'' oncologist from UPMC offered THIS advice. ''This cancer is nothing but a play for time. There will be new drugs coming out down the pike. Wait for and take the NEXT best drug and hang on as long as you can.'' Of all the advice we've received, and believe me, we sought some of the best with trips to Sloan and Dana-Farber, Johns Hopkins...those two docs gave us the best advice. He's now 69 years old and despite his rising PSA, is still living a decent life on 45 mg of oxycodone as needed. He said the oxy stopped making him too high to do anything within a week of taking it, We're keeping our fingers crossed on the Xofigo. We were warned it might not help as well with bone mets pain as IMRT spot radiation does, but it should offer some life-extension. Hopefully, he can also benefit some from Darolutimide should he be able to obtain it early, or survive long enough for FDA approval. We've seen a lot of guys come and go during his 12 years of treatment, many with less aggressive cancers than his. We followed the ''old timer's'' advice. They didn't.

[Hidden]

Xtandi is an anti-androgen, so it would make sense to have the test, instead of wasting tens of thousands of dollars on a drug that isn't going to do anything for you. If the test would come back positive, I then think one would be put on some type of Taxane based chemo.

Zytiga, on the other hand, is a hormone based chemo. As with Lupron, it just stops working after it's run. I believe this is the way it works.

Joe