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Metastatic (M1), but still hormone sensitive (mHSPC) - best options

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Posted 6/6/2017 8:38 PM (GMT 0)
There have been several recent threads about the two new trial results concerning early use of Zytiga. Since this is a subject of great interest, I put together a blog of what I know about the treatment of men with metastatic hormone-sensitive PC. Not just with Zytiga, but with all the other options currently being explored. I threw in links to the clinical trials I know about, and I'll try to keep them updated.

/pcnrv.blogspot.com/2017/06/newly-diagnosed-metastatic-m1-but-still.html
Posted 6/7/2017 1:57 AM (GMT 0)
Thanks Allen. Awesome write up.

I was just about to post about how effective Xtandi might be in combination with HT for hormone sensitive patients. The results of the recent Zytiga study are awesome, but it may be that Xtandi might also show comparable results...I guess TBD.

I'm always looking for what to throw at it when I come off my HY vacations, and your write up is a good reference.
Posted 6/7/2017 2:57 AM (GMT 0)
Really interesting and useful information. -Thanks Allen
Posted 6/7/2017 5:10 AM (GMT 0)
I suspect apalutamide will be the new one to beat. Wouldn't it be nice if they had a randomized trial of Zytiga vs Xtandi, or Xtandi vs apalutamide? Drug companies will never go for it.
Posted 6/7/2017 11:19 AM (GMT 0)
For reference, Apalutamide is ARN-509. I think the last word was approval by 2019.

It would be nice to put these head to head to see which is more effective and in what setting. Even nicer would be that we figure out how to eliminate the cross resistance so we could get the most out of each.
Posted 6/7/2017 11:33 AM (GMT 0)
Great summary, and definitely of interest to many of us! Thanks for all the time it took to put that together. That link needs to go in the list of stickies on the forum.
Posted 6/7/2017 3:30 PM (GMT 0)

Tall Allen said...
I suspect apalutamide will be the new one to beat. Wouldn't it be nice if they had a randomized trial of Zytiga vs Xtandi, or Xtandi vs apalutamide? Drug companies will never go for it.

Isn't darolutamide another antiandrogen in phase III that might be even more potent than apalutamide for CRPC? Have you seen repors about darolutamide? Would be interesting to understand hove these next generation antiandrogens works, is possible to explain shortly?
Posted 6/7/2017 5:36 PM (GMT 0)
This is interesting news, but I am wondering if we move some of these treatments up for earlier use, do we lose as I put it, bullets in the gun? Without a cure, it is really about extending our good quality of life as long as a possible. TA has anybody looked at the treatment combinations vs. longevity?

Just curious.


Mike
Posted 6/7/2017 6:28 PM (GMT 0)
Gemlin -
Yes - there is a link there to the darolutamide trial. It is only recruiting so far in a couple of sites. They are only testing it in combination with docetaxel. I hope it works well.

Mike-
Perhaps I don't understand what you're saying. All of those trials demonstrated significant benefits in overall survival by using it earlier. That was the whole point of those clinical trials. If you read the article, it is addressed.
Posted 6/7/2017 7:16 PM (GMT 0)
Mike,

I understand, in part, what you're saying about losing bullets in the gun. In this recent study, it appears that firing off the Zytiga bullet (in conjunction with HT) earlier will keep the beast away longer vs. firing in sequence. It's sometimes tough, however, to choose these newer therapies knowing that there are less options down the road. But it's not logical. Get the most out of the proven drugs as soon as they prove themselves in the earlier settings.

I've always been of the belief that combination therapies will give the most benefit. Look at HIV and other diseases. These are controlled by adding several different therapies at one time vs. single agents one after the other after they fail.

This recent Zytiga study was a study in combinations vs. single agent hormone therapies (I think). I'm not sure if the HT that was being used was ADT3 or not for example.

As far as quality of life...I wonder if those that took the Zytiga early didn't in fact also have a better quality of life given the better disease control.

Thanks,
JL
Posted 6/8/2017 11:03 AM (GMT 0)
Thank you again Allan for sharing your knowledge.

The more information a mind has the more it can see things with depth and in stereoscopic 3D.

Much appreciate it!

about the Zytiga trial, you mentioned that participants were on it for an average of 2 years. Is there any data on how long till recurrence after treatment?
Posted 6/8/2017 5:16 PM (GMT 0)
In the LATITUDE trial, the median length of radiographic progression-free survival (radiologic or death from prostate cancer) was 33 months in the abiraterone group and 15 months in the placebo group (hazard ratio=0.47). The median length of time until PSA progression was 33 months in the abiraterone group and 7 months in the placebo group (hazard ratio=0.30).

In STAMPEDE, among men with metastases, median failure-free survival (radiologic, clinical, or PSA progression or death from prostate cancer) was roughly 54 months in the abiraterone group and 12 months in the placebo group (hazard ratio=0.31).

(LATITUDE recruited patients with higher risk characteristics than STAMPEDE)
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