AR-V7, Zytiga(abiraterone) and Xtandi (enzalutamide)

[Cmdrdata]

According so some studies, 40-50 percent of patients receiving any of the above drugs do not respond well or develop resistance in about one year. I am curious to know if any of you who are already taken these drugs know whether you have been genetically screened for the presence or absence of AR-V7 prior to taking the drug and the resultant PSA response. See ascopubs.org/doi/full/10.12... these drugs depended on the absence of AR-V7 to be effective.

[Hidden]

Data:

Very good questions. It is my understanding that patients are nor routinely screen for androgen receptor variants. Recently they have not found association with the presence of AR-V and resistant to abiraterone and enzalutamide.

Expression of Androgen Receptor Splice Variant 7 or 9 in Whole Blood Does Not Predict Response to Androgen-Axis-targeting Agents in Metastatic Castration-resistant Prostate Cancer.

To SQ1, Kwan EM2, Fettke HC1, Mant A3, Docanto MM1, Martelotto L1, Bukczynska P1, Ng N4, Graham LK5, Parente P6, Pezaro C6, Mahon K7, Horvath L8, Todenhöfer T9, Azad AA10.

Author information

Abstract

In 2014, a landmark study was published demonstrating that the expression of androgen receptor splice variant (AR-V) 7 was a negative predictive biomarker for response to abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. However, these results were not supported by the recently reported ARMOR3-SV phase III clinical trial, which employed an identical circulating tumour cell assay to assess AR-V7 expression. Therefore, the predictive utility of AR-V7 expression in mCRPC remains uncertain, as does any potential association between other AR-Vs and treatment response. To further investigate, we designed a highly sensitive and specific whole blood assay for detecting AR-V7 and AR-V9. We then examined for a correlation between baseline AR-V7/V9 status and treatment outcome in 37 mCRPC patients commencing abiraterone or enzalutamide. Of the patients, 24% (9/37) were AR-V-positive. Notably, prostate-specific antigen (PSA) response rates did not significantly differ between AR-V-positive (6/9) and AR-V-negative (18/28) patients (66% vs 64%, p=0.9). Likewise, median PSA progression-free survival was not significantly different between AR-V-positive and AR-V-negative patients (9.2 mo vs not reached; p=0.9). These data, which support the findings of the pivotal ARMOR3-SV clinical trial, suggest that baseline AR-V expression does not predict outcomes in mCRPC patients receiving abiraterone or enzalutamide.

PATIENT SUMMARY:

Detection of androgen receptor splice variants (AR-Vs) in circulating tumour cells of advanced prostate cancer patients has been linked to resistance to abiraterone and enzalutamide. We designed a blood test to detect AR-Vs that can be performed more routinely than tests involving circulating tumour cells and found that patients with AR-Vs still benefit from these effective treatments.

[kaptank in reply to Hidden]

On the other hand, evidence is accumulating that ARV7 has some role in resistance.

healthunlocked.com/advanced...

[kaptank in reply to kaptank]

sorry, I didn't realise this was a year old thread. ADT brain.

[charmander]

Nal,

I seem to remember that you posted where you purchase your BIM. Would you mind letting my know your preferred source? Thanks Charlie

[charmander]

Thanks Nal! The cancer inside me seems to galloping at the moment. Went thru zytiga and xtandi and 6 cycles of docetaxel. While on Doce my lymph nodes in my chest were determined to now be involved with enlarged nodes pushing against my lung. Am currently on cycle 2 with cabazitaxel with much fewer side effects. My goal is to be able to participate in my daughter's wedding at end of September!

I've always been impressed with your posts and the knowledge they embody. I'm so glad your program has worked so well for you. I also hear your reluctance to offer advice. Am wondering however if you would mind reviewing my supplement list and hypothesizing on any changes. If this is something you'd be interested in then I would send you my stats and supplement list. I know this is a big ask considering what you've written before.

Charlie

[Magnus1964]

I was told that you go through the list of ADT drugs, each one will have a shorter time of efficacy. Which seem to be true in my case. Casodex was effective for 5 years, Aboratorone, lasted 3 and 1/2 years, I am currently on xtandi and it has been effective now for 2 years, don't know how much more I can get out of it.

[rust]

AR-V7, hmmm? Makes me wonder if I should get typed before I go the trouble of entering EMBARK clinical trial next week. My PSADT is currently 2 months over last 12 months and BCR after being 0.02 for 4 years after SRT in 2013. Also wondering about Estradiol supplementation or as a substitute for Leuprolide.

[Cmdrdata in reply to rust]

Rust, as in many clinical studies, it seemed that there are other researchers that dispute the impact of AR-V7 (see link shown by other member of this group in subsequent posts). All we know is that not everyone on Zytiga/Xtandi respond favorably to these drugs. Similarly, the subject of estradiol is controversial. I read articles that in men, estradiol is an agonist (promoter) to prostate cancer growth, in the absence of testosterone. The EMBARK study is pretty benign, and if you haven’t been on ZYTIGA or XTANDI, should be considered, as they provide access to you on these relatively new drugs, which cost a ton if you were precribed normally .... Good luck and read this about estrogen (in other word, estradiol): ncbi.nlm.nih.gov/pmc/articl...

Julius

[Cmdrdata in reply to rust]

One other thing, it is MY belief that T-suppression, AR and similar drugs are just stop gaps in controlling prostate cancer growth but not really eliminating it for good. My hope is that genetic based treatment that awakens our immune system to fight our cancer is the one that will finally provide us a cure. PTEN and PARP studies (like this: ncbi.nlm.nih.gov/pubmed/292... I think is the key to our future survival from prostate cancer.

[Kevinski65]

Not all insurance covers genetic testing. I wonder if ordinary Medicare pays for it.

[Cmdrdata in reply to Kevinski65]

Kevin, I don’t have that info. I am on Medicare, but have never been genetically tested. Perhaps someone here with Medicare that has gone through this testing will be able to answer. Sorry.