So, after my brothes failure of ARV -110 with an initial big drop in PSA and then steady climb back up, we just received another report from Foundation One that shows growth in the initial mutations along with several other newly developed mutations. His Dana Farber doctor has decided to put him on Darolutimide. There have been no clinical trials in mCRPC. He has started it already. Looking ahead, she said he may be a good candidate for keytruda because of the very many newly developed mutations. We have asked for a copy of the genetic report so that we can see which mutations specifically she is hopeful about. He is not MSI or BRCA. Perhaps something in the DNA repair mutations. So, a complete turn around as he will not be starting the PT 112 trial. And the journey continues .........
The roller coaster ride with its twis... - Advanced Prostate...
The roller coaster ride with its twists and turns continues...
There was this one:
thelancet.com/journals/lano...
Interesting TA I was unable to find any trials for mCRPC. You always come up with something! Interesting that it has a good safety profile and some disease suppression. I wonder why they never pursued clinical trials for mCRPC. It seems that when used for non-metastatic it doesn’t develop the mutations that are seen with Zytiga and Xtandi. I wish I knew this when my brother finished Docetaxel before starting Zytiga.
There are a couple of ongoing clinical trials for darolutamide in mCRPC, but they are both in Europe.
Why do you say that it doesn't result in the same mutations seen with Zytiga and Xtandi in non-m CRPC? I must have missed that - do you have the study that looked at that? That would surprise me. In fact, I haven't seen anything about the mutations seen after Zytiga or Xtandi (or Erleada) when used for non-m CRPC.
Cancers mutate readily - it's what they do.
I am sorry if I misinterpreted the following study. I certainly wouldn’t want to mislead anyone. Thank you for bringing it to my attention. I am not a geneticist or doctor and it is sometimes overwhelming reading through the myriad of information out there. The following is what I read.ncbi.nlm.nih.gov/pmc/articl...
My thinking was that my brother had two of those mutations and if the ARV 110 trial degraded them would Darolutimide be a viable option going forward even though it is not approved in mCRPC.
“One interesting characteristic of darolutamide that has yet to be thoroughly investigated in a clinical setting, is the fact that it has been shown in preclinical studies to block the effect of multiple mutant ARs, including F877L, W742C and T878A.10 This certainly could be interesting to investigate in patients who may harbor these mutations, and who may have progressed on other androgen- or AR-targeted therapies”.
urotoday.com/clinical-trial...
I hope it is effective for him. The way I interpret what the article is saying is this:
The AR naturally mutates at several different sites or those mutations may have been there from the start. Those mutations may include F877L, W742C and T878A. Other antiandrogens (bicalutamide, enzalutamide, and apalutamide) activate ARs that have those mutations, whereas darolutamide does not. None of the anti-androgens cause those mutations, but it is hoped that because darolutamide won't activate ARs that already have them, those cancer cells will be less active. This hasn't yet been demonstrated clinically, as you say.
Thank you TA for clarifying that. It helps me understand things a bit better especially when speaking to his doctors. I always learn so much on this forum.
I understand that for Keytruda to be effective, the patient needs to be MSI and have a high tumor burden, neither of which I have.
I know it's apples to oranges but Keytruda is working for my Lung Melanoma...... Keep the Faith, Faith.....
BTW your brother has a good looking sister.........
Good Luck, Good Health and Good Humor.
j-o-h-n Tuesday 03/09/2021 12:07 PM DST
Thank you John. I am so happy you are having good results with Keytruda. I enjoy your humorous posts!
Where's Bob, we used to talk by phone, but not heard from him for awhile. We're both cared by Dana-Farber, always enjoyed the high energy talk. 
Bob’s doing pretty good. I will let him know you’d like a phone call! I’m sure he’d love to talk to you
I will be interested in hearing how he does on the Darolutimide. I will also be starting Darolutimide in a few days, and I am also mCRPC. My mets are currently lymph node only, but they have moved further up to the para aorta area. I am just coming off a nice drug holiday after 3 years of hell with Firmagon and Eligard injections with a smatering of Xtandi. I will be giving Darolutimide a try as a monotherapy, as I did not tolerate the chemical castration drugs well at all. fingers crossed we both have good luck with Darolutimide.
Joe, How is the nubeqa working for you now?
Initially it took PSA from around 5.0 down to .90, but its been steadily creeping up since. Yesterdays reading was 2.90, so looks like Im going to have to add Relugolix to the nubeqa, and hope I dont have the cardiac and cognitive problems I had before when I was on Firmagon & Xtandi
Hi joeguy, Bob has been on Darolutimide 11 days and his PSA dropped four points. He unfortunately has quite a few bone Mets. He feels pretty good on Darolutimide with no side effects. He has already done Zytiga, Xtandi, Provenge and Docetaxel and a clinical trial of ARV/110. The clinical trial saw his PSA plummet rapidly which we were excited to see but then proceeded to rise quickly which ended the trial. So the game plan is now to stay on Darolutimide as the PSA continues to drop. Next step will be Keytruda however I’m hoping that is way in the future! Best of luck to you and keep us posted. I am very interested to see how you fare on Darolutimide as well. Hopefully many years undetectable!
Faith, How is darolutimide working for Bob? It's been 10 months now.
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