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Xtandi/Zytiga resistant? AR-V7 may be reversible

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Posted 6/29/2015 7:02 PM (GMT 0)
A genetic variation of the androgen receptor, called AR-V7, has been implicated as one of the factors (there are many more) that are to blame for resistance to Xtandi or Zytiga. When someone has this genetic mutation, Xtandi and Zytiga never work well from the get go (as opposed to failure after some longer time).

A new study from Johns Hopkins, where AR-V7 was discovered, finds that it may change over time. Among 14 mCRPC patients who were found to be AR-V7 positive at some point during various therapies,
• 3 were AR-V7 positive throughout
• 8 converted from AR-V7 negative to AR-V7 positive
• 6 converted from AR-V7 positive to AR-V7 negative - all during therapy with Taxotere or Jevtana!
(a few patients apparently went back and forth over time)

This may be really good news for some of us - genetics is not destiny and may be changeable.

If any of you have been told that Xtandi/Zytiga is useless for you because you have the AR-V7, show this to your oncologist. It's possible that a round of chemo may reverse that and re-sensitize you to Xtandi and/or Zytiga.

Serial Blood-Based Analysis of AR-V7 in Men with Advanced Prostate Cancer

- Allen
Posted 6/29/2015 7:13 PM (GMT 0)
That's really interesting and good news! So, potentially for some people, they could respond to Xtandi/Zytiga, then develop resistance, switch to Taxotere, develop resistance, then try Xtandi/Zytiga again?

And taking into account that tests for AR-V7 are being actively developed, this back and forth could be made more precise by first testing for the presence of this generic variation.

This is very encouraging news!

Thanks for sharing.

Arthur
Posted 6/29/2015 8:06 PM (GMT 0)
I agree, Arthur. I don't want to overpromise, however. A lot of men will become resistant to Zytiga/Xtandi without ever developing the AR-V7 variant. We should also keep in mind that only 14 patients were watched in this study.

I think the commercial availability of an AR-V7 test may be some time off. Meanwhile, some oncologists may want to re-challenge Zytiga/Xtandi-resistant patients with Taxotere or Jevtana.

- Allen
Posted 6/30/2015 1:47 PM (GMT 0)
This is interesting. Husband was on zytiga, Xtandi and LUPRON. Since November. 14. pSA continued to rise. Scans show tumor progression he was also in a lot of pain. No bone mets. They took him off Xtandi, but continue Zytiga& LUPRON shots. AND, began chemo. This time. jevtana/Carboplatin combo. Has had two treatments. Will do scans next week to see how tumors are responding. Would it be worth asking about the AR-V7 test to try these meds.again after chemo if progression begins again?
Posted 6/30/2015 4:54 PM (GMT 0)
There is no commercially available AR-V7 test, unless he's being treated at Johns Hopkins. With AR-V7, neither Xtandi nor Zytiga work. And regardless of AR-V7 status, Xtandi and Zytiga often create cross resistance. Worth a discussion with his oncologist anyway. Has he tried an estrogen patch?
Posted 6/30/2015 5:19 PM (GMT 0)
Good interesting thread Tall Allen. I have been on Zytiga since last August and asked about switching to Xtandi today on my visit. He advised not to because Zytiga is still working, and why chance messing that up. PSA is 4.2, down from 4.5 last month. It is good to know that there is a chance these drugs can start working for someone with after a chemo session.
Posted 6/30/2015 6:13 PM (GMT 0)
Faustmann,
What about using them at the same time? They attack the androgen receptor from different angles, and that may slow down its resistance.
Posted 6/30/2015 7:21 PM (GMT 0)
Xtandi + Zytiga at the same time? I doubt insurance will do that. These drugs are expen$ive !
Posted 6/30/2015 7:24 PM (GMT 0)
Sanofi just announced a clinical trial starting in August that seems to be looking at this phenomenon:

Cabazitaxel Versus the Switch to Alternative AR-targeted Agent (Enzalutamide or Abiraterone) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients Previously Treated With Docetaxel and Who Rapidly Failed a Prior AR-targeted Agent (CARD)
Posted 6/30/2015 7:28 PM (GMT 0)
The combo is available on some clinical trials.
Posted 6/30/2015 11:22 PM (GMT 0)
i go for scans monday the 6th of july.i am being placed in a clinical trial for the combination of xtandi and zytiga,along with prednizone if i draw,or rather the computer draws the side with both. my psa has risen over 3 points since the middle of may.i will continue to get the trelstar shot every 24 weeks as well.
Posted 7/1/2015 1:54 AM (GMT 0)
Mickey,
my husband has been on the combo Zytiga/Xtandi Prednisone + 3mo. LUPRON shot since Nov. 2014. Not part of a clinical trial. Insurance has covered it. (BCBS).
Might be worth looking into.nsure wouldn't hurt. I will say the Xtandi side effects were pretty tough. Lots of fatigue and muscle aches. No appetite. But, I have read it does like Tall Allen mentioned.
Posted 7/1/2015 2:02 AM (GMT 0)
Allen,
I had not heard of them using Estorgen patches. What is the purpose. And effect it is to do? I will bring it up with his Oncologist next week.
Thank you so much for the information. Always trying to be ahead of the next "bump in the road" good news PSA has come down from 14 to 10 after just 1 treatment of Jevtana/Carboplatin. He never has had a high PSA. I think highest was 49 at diagnoses. Lowest was .50 after 6 rounds of Taxotere/Carboplatin last yr. slowly crept up after about 3 mo. Progression of mets is biggest concern and pain in back, pelvis and abdomen due to size. Got to keep them knocked down. Have a great evening everyone.
Posted 7/1/2015 2:19 AM (GMT 0)
Estrogen is an old hormone therapy for PC that's getting is getting a second look. It was dropped over concerns about blood clots, but the patches don't seem to create that problem the way pills do. It works in a similar way that Lupron does - the pituitary reacts to the excess estrogen by shutting down androgen production. There are several different kinds of estrogen used for this purpose.

Below is an article about it. There's a large-scale clinical trial in the UK now comparing the efficacy and side effects of estrogen patches to drugs like Lupron:

Low-dose diethystilbestrol in treatment of men with CRPC

Prostate Adenocarcinoma: TransCutaneous Hormones, PR09 (PATCH): A randomized controlled trial of transdermal estrogen patches versus luteinising hormone releasing hormone agonists in locally advanced and metastatic prostate cancer.
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