clinical trial olaparib and radium 223

[Judymin]

my husband has been fighting this beast for 10 yrs. Chemo/ADT/zytiga now this new trial. We are waiting for scans next month but psa jumped to 60!!!! I asked doctor about this, he said that is only one small part, scans important part and how he feels. He feels good, has had no pain at all. Last scans showed small mets in clavicle/ribs which is why 223. He has had only lymph node mets prior which are very small. My question...should we continue this trial. To me it looks like failure. They did biopsy of lymph, not sure what it showed. Prior gardant blood test showed no BRCA 1 or 2 only ATM. Any thoughts appreciated as very frustrated and terrified. judy

[Hidden]

"I asked doctor about this, he said that is only one small part, scans important part and how he feels. He feels good, has had no pain at all."

Good signs and I would agree with your doctor to continue. PSA is only one indication and as my doctor says: "We are treating the cancer, not the PSA". You also have to look at what other options are if you decide to stop. The "then what" question.

How is his ALK PHOS? That's another blood test that can give you an indication of turnover in the bones that often indicates an increase or decrease in the activity of bone mets.

[Tall_Allen]

I think it's a promising trial. While PARP inhibitors don't work well as a monotherapy unless there is a BRCA mutation (germline or somatic), and Ra-223 works best against smaller bone metastases, the hope is that combining them will kill the cancer cell when there is sublethal DNA damage from Ra 223. Here are the combinations with Ra 223 that are being tried:

prostatecancer.news/2021/02...

Of course, the Ra223 will do little for the lymph node metastases. A similar combination is being tried in Australia, combining Lu-177-PSMA and a PARP inhibitor.

You may also want to look into the the Th-227-PSMA trial. Th-227 decays into Ra-223. When it does, Ra-223 may detach from the PSMA ligand and goes after the bone metastases. So it can kill cancer cells in both the bones and the lymph nodes with powerful alpha radiation.

[Patrick-Turner in reply to Tall_Allen]

It is again interesting what you say about Thorium 227. I am having Ra223 now because docs concluded I have no soft tissue mets in lymph nodes or elsewhere, and I only have bone mets. Docs are saying its highly unlikely any of my newer bone mets will generate PsMa avidity in future, but afaik, I did have some older bone mets in last PsMa scan which did have PsMa avidity. But theory is that Ra223 should take out all my bone mets without any reliance on PsMa expression. What I really cannot know until I have scans a little later is that there may be new soft tissue mets which have grown up big enough to see in scans, and these may not make PsMa so Thorium 227 when guided by PsMa ligand would not do anything, and my DNA tests of blood in Nov 2020 showed I have no Brca1+2 or anything else that could lead to a best way to treat whatever is found, so olaparib would be useless. The age old problem of fighting Psa is vexing because the Pca mutates, and just because it looks like all soft tissue mets are gone, there could be new mets forming as I write, and I have zero idea of what could be done, except use of chemo, which in my case seemed to be a dismal failure when tried in 2018. But if any new visceral mets did have *enough* PsMa avidity, and not all bone mets were fried, then Thorium may be a good 2 in 1 solution.

I'll head out for a nice bike ride tomorrow, autumn weather is truly glorious, and I have only to finalize re-building work on a tube amp I made in 1994, and so life continues OK despite so many uncertainties.

Patrick Turner.

[Tall_Allen]

Because not very potent with ATM, although approved.

[wpopomaronis in reply to Tall_Allen]

Oh my very smart and good man, what do you think about the impact of this combination on someone with Chek2 mutation. I’m afraid to tell you what my PSA is now but after Lutetium dropped it all the way down to 36 from 93 in 8/2021, this aggressive cancer moved all the way up to 2003 PSA in 6 month. I’ve battled Gleason eight cancer for 13 years. I know I’m a dead man walking but I keep hanging in there because of my children and hopes that I can be here long enough for something to extend my life. I wanna tell you that I’ve learned a lot from you and appreciate you. May God‘s blessings be upon you all.

[Tall_Allen in reply to wpopomaronis]

PARP inhibition for CHK2 mutations is underexplored. There were only 3 men with that mutation in the TRITON2 randomized trial of rucaparib, and it curtailed radiographic progression in 2 of the 3 for 6 months. But a clinical trial presented today found that combining Zytiga with Lynparza was effective regardless of whether they had any kind of DNA damage repair mutations.

[wpopomaronis in reply to Tall_Allen]

Thank you

[Patrick-Turner]

If I was a Beta man, would I qualify to become an Alpha male?

Hoo Noze?

Patrick Turner.