Post triple therapy options?

[TK934]

This past summer, I wrote because my husband's PSA numbers started doubling very quickly. (see quick recap below) By the time we got the PSMA PET scan a few weeks later, there were too many tumors in the bones to count. We jumped into triple therapy: Eligard, Nubeqa, and chemo. David's last chemo (6 rounds every three weeks) was 2 weeks ago, and the testosterone levels dropped immediately to nearly zero. The PSA numbers came down gradually, but seem to be stalling around 1.3. (Three weeks earlier it was 1.5). My impression was that the PSA should ideally be close to zero, and I'm concerned that the 1.3 level may reflect some castrate-resistance and active tumor(s).

In the next seven days, David will have CT, PSMA PET and bone scans. On February 5th we will meet with the medical oncologist. I'm hoping to be prepared for the discussion of what the next steps might be.

I know the plan is to continue with the Eligard/Nubeqa as long as possible. And if the PSA remains stable, that would be ideal. However, if there the PSMA PET scan shows active tumors, I'm thinking of the following options, and would love your collective input. Also, are there other possibilities I'm missing?

1. Actinium 225. This used to be available in Australia (where we had the Lu177 treatments), but it doesn't seem to be currently available. Also, I read about the tandem study which combined Act225 with Lu177 (the idea being that the Lu177 could go after the larger tumors and the Act225 could go for the super small ones), which seems promising. We know about the concerns for the saliva glands. Is there someplace that is doing the tandem treatments? or even just Actinium?

2. Terbium-161. This seems to be a substitute for Actinium 225. I don't know much about it. However, it is available in Australia. (Our consult with our Australian doctor is Feb 7th).

3. Xofigo Radium-223. This seems to be specifically for bone mets, which is all that showed up for David's PSMA PET scan five months ago. And since then, he's been on the triple therapy. (Weirdly, no tumors were listed in the lymph nodes --- was that the Lu177-J591 still being effective?) I've read some of the posts on this, and it seems like Xofigo can stop the bone tumors from growing, but it doesn't eliminate them. Happily, it is available here in Ottawa.

With thanks ....

A very quick recap: Diagnosed in 2013, started with "active surveillance". Focal (ICE) treatments to the prostate, Lu177 treatments (which worked really well for 4+ years!), then radiation for three lymph tumors and one rib tumor followed by Lu177/J591 in 2022.

[tango65]

Triple therapy has been shown to offer a survival advantage only in the novo metastatic castration sensitive cancer. I am not aware of the benefits of doing this therapy when a cancer has been already treated with Lu 177 PSMA and radiation,

If and when there is a radiologic evidence of progression of the cancer there are many therapies and clinical trials available such as xofigo, provenge, parp inhibitors (olaparib, rucaparib, talazoparib) alone or in combination with zytiga or enzalutamide.

Ac 225 is a possibility particularly the one form of Ac 225 using the J591 ligand since it seems to affect less the salivary glands. There are clinical trials recruiting at this time.

Then there are clinical trials with the new ""antiandrogens"" (protacs) such epi-7386, ONCT 534, ARV-766 etc. etc.

Consider requesting a direct or a liquid biopsy (such a Guardant 360) to determine the genome of the cancer and see if it could respond to PARP inhibitors or to Keytruda.

[TK934 in reply to tango65]

Thank you for this. Lots more for me to look into. I looked at one of the Ac225/j591 trials (my husband is Canadian, but he does have US Medicare), but it seems he would be excluded because of previous Lu177/J591. Perhaps it's still worth asking? I'll keep looking! Thanks also for the new information on the new "antiandrogens". And I will definitely ask about the biopsy. You've given me a lot to learn! I'm very grateful.

[tango65 in reply to TK934]

I wish you the best of luck with the treatments and I hope it will take a long time to show a radiographic progression. One treats the tumor and not the PSA.

[TK934]

Thanks! I know we will know more after the scans ...

[countrymusic101]

Hello- I have an answer to one of your questions.

This clinic in Vienna does actinium and Lu-177 combo treatments.

minute-medical.com/en/team/

[TK934 in reply to countrymusic101]

Thank you!

[hansjd]

May I ask which doctor in Australia you will be consulting with? Also where did your husband have his Lu177 treatment in Australia? Thanks

[TK934 in reply to hansjd]

David had his first Lu177 in Sydney with Dr. Nat Lenzo, which was quite successful. At the time he had three lymph mets, and after the two treatments, he was clear on PSMA PET scans for over four years. The second visit was in Perth was Lu177/J591, but at that time there was one met on his rib in addition to lymph mets (which was radiated in advance of the Lu177/J591). Unfortunately, about a year later, the bone mets came back ( really fast!). We have a consultation with Nat booked for next week. I should mention that David did Lu177 before any hormone therapy. We always put off the hormone therapy as something we could do later (and that's where we are now). But it worked out for us. There are now trials with this approach.