Updated treatment plan for progressing MCRPC

[Islandboy2021]

I have started Xgeva and also was able to get a prescription for Estrogel Transdermal gel.

Will start Xofigo Radium 223 that was approved last week.

I am still taking abiraterone and dexamethasone and it is not working, PSA has been climbing.

My Question is, should I switch the abiraterone for enzalutamide. There is some evidence for switching these drugs if one is no longer working. Apparently the dexamethasone is not good for bone health.

Xgeva every 3 months, Xofigo every month for 6 months and possibly add enzalutamide.

What do you think of this plan,

Thanks,

[Tall_Allen]

Your PSA is still quite low, so don't give up yet on the abiraterone+ dexamethasone. The corticosteroid is just a replacement dose for the lost cortisol and so it shouldn't affect your bones.

Xgeva should be monthly, not every 3 months - especially important with Xofigo.

[Islandboy2021 in reply to Tall_Allen]

PSA is at 6.45 and climbing.

Still continuing with abiraterone. Can I continue with the abiraterone once I start the Xofigo.

The bone specialist said there was a study done in Australia stating that Xgeva every 3 months was fine. I will have to change the prescription for Xgeva.

Thanks

[Tall_Allen in reply to Islandboy2021]

Sorry. I was going by the PSA in your profile (0.18). In that case, I think you are right to switch to enzalutamide.

Every 3 months was equivalent to monthly with short follow up. I think monthly is needed with Xofigo, which is what was done in the clinical trial.

[Islandboy2021 in reply to Tall_Allen]

The Oncologist has confirmed that the SOC here in BC does not support enzalutamide after failure of abiraterone or during treatment with Radium 223. Apparently having enzalutamide during Radium 223 creates or promotes possible bone fractures.

If I want to use it I will have to pay for it.

[Seasid in reply to Islandboy2021]

Save enza for later

[Hidden in reply to Islandboy2021]

Island boy, our research MO says the same thing as yours. My husband gets Xgeva every 3 months. Says every month is “not necessary”.

[Hidden in reply to Hidden]

journals.sagepub.com/doi/fu...

[dhccpa in reply to Hidden]

Is he on Xofigo, though? That might make a difference.

[Hidden in reply to dhccpa]

No, he is on denosumab (brand names Xgeva and Prolia). He has bone and a lot of lymph Mets so not really a candidate for Xofigo. Take a look at the link. To sum it up, the authors wrote, “In conclusion, extending denosumab dosing intervals beyond 4 weeks did not appear to negatively impact time to first SRE or mOS in solid tumor patients with bone metastases.”

[Tall_Allen in reply to Hidden]

They only had 2 years of f/u. There is a clinical trial now to determine what happens with longer f/u.

clinicaltrials.gov/ct2/show...

Hopefully, we will have results by the end of the year.

Meanwhile, Fred Saad warns against dose de-intensification:

"We did an analysis looking at different centers in Canada, some that give every three months and some that give every four weeks, and we saw that patients that were getting it every three months that needed it, were actually having almost the same event rate as patients not treated at all."

urotoday.com/video-lectures...

[Islandboy2021 in reply to Tall_Allen]

I have got the bone specialist to change prescription of Xgeva injection to every month

[Hidden in reply to Tall_Allen]

The studies you link are older de-escalation studies that don't apply to islandboy and my husband. That's a different group of guys. They started with 4 week injections and tried to scale back (de-escalate) to 13 week injections. Our MO recommends starting with a 13 week dose. I think doctors are realizing long term use of bone modifying agents have their own nasty can of worms and are trying to lessen long term consequences. Stopping denosumab appears to be at least as harmful for bone events, if not more harmful, than never taking it at all. And de-escalating from a 4 week treatment cycle to a 13 week treatment cycle appears to also be detrimental.It makes sense to us--and my husband's docs-- to minimize exposure to the drug's harmful side effects from long term use while still receiving benefit.

e-enm.org/journal/view.php?...

Also, Fred Saad (the doctor in your video link) "serves as a consultant, advisory board member and received honoraria and research funding from Amgen", the company who makes Xgeva. The connection makes me a bit skeptical of his partiality.

Finally, a more recent report than yours concludes: "A retrospective study of denosumab based on dosing interval (< 5, 5–11, or ≥ 12 weeks) found that time to first SRE and median OS were not significantly different with extended dosing schedules [82]."

ncbi.nlm.nih.gov/pmc/articl...

I really think it is one of those drugs they just haven't figured out what dose interval is best. It didn't matter when men with bone mets didn't survive more than 2-5 years. But now that the treatment options have expanded and metastatic men are living longer, the dosages they thought were best 10 years ago when the drug was introduced is now proving to have its own set of unintended consequences.

[Tall_Allen in reply to Hidden]

Fred Saad is one of the most respected oncologists in the world, and he knows more about bone strengthening medicines than anyone.

I'm sure AMGEN didn't influence him to propose that that these agents be limited to 2 year intervals. And don't you think Amgen would have been happier if he had just said Xgeva was better at reducing SREs than Zometa, instead of observing that they are equivalent if given at similar intervals?

The link you gave was for a 2020 retrospective study (not more recent). Irrespective of its date, the problem with such studies is selection bias - the people who were given the more intense dosing were the ones judged to need it more. That's why we have to have randomized clinical trials like the one I linked.

A new analysis of STAMPEDE given at the AUA conference last week, found, for the first time, that Zometa, used monthly while metastatic men are still hormone-sensitive, prevents fractures. This, combined with the STAMPEDE trial that found a survival benefit of Zometa + Celebrex in newly diagnosed, men with bone metastases, argues for earlier intensive use of Zometa.

[Seasid in reply to Tall_Allen]

I don't believe that we should just simply stop Xgeva after 2 years?

It would be dangerous and could result in broken bones. That is my understanding of what I was told by the endocrinology. And that is the main reason that I may choose Zometa instead in order to avoid fracture related to stopping Xgeva.

I am really confused now. I don't believe that Fred Saad would suggest suddenly stopping Xgeva after 2 years if it could cause bone fractures.

István

[Tall_Allen in reply to Seasid]

I think he means - one should take a break after 2 years, and resume after the break. I think his logic is that the worst side effects, like ONJ, are cumulative, and it is necessary to do a re-set periodically. Here is exactly what he said:

"And you and I have heard many people say, "Well, maybe we don't need to treat them that intensely. We can maybe spread out the number of doses." And we actually did it in several analyses, and when you dose de-intensify, the risk of these events increases significantly and so, I think in that state, every four weeks remains important. The question is how long? And, obviously, people are worried with long exposures of osteonecrosis of the jaw, among other issues, and so personally, after two years, we take a step backwards."

[Seasid in reply to Tall_Allen]

All of these is definitely a big headache.

If you take long term Zometa like lot of ladies with breast cancer you could end up with atypical fracture of the femur.

I believe in a Stamped trial there was no difference in a survival of patients on Zometa in comparison with patients without Zometa but all that patients lived relatively short.

Coleman said that there is no advantage of taking zoledronic acid if you are metastatic. It will not make a difference on the development of bone mets. It will not stop the development of the bone mets.

Of course if you are osteoporotic and your bones are weakened by the mets, than you should consider to take bone strengthening medication especially if you are CRPC and planing to get Xofigo. You could avoid compression fractures of your spine plus fracture related to the alpha radiation coming from Xofigo which could end up everywhere in your osteoporotic bones.

Maybe the best cause of action is wait until you see that you will need Xofigo and than use the maximum dose of bone strengthening medication up to 2 years and then stop.

One more thing what I believe it is important to realise is that because you are taking bone strengthening medication plus Xofigo you are actually not preventing the cancer nor you are preventing the popping out new bone mets during Xofigo. Xofigo only repair the current bone mets under certain circumstances. Xofigo will not fight the cancer in your body it may only repair the damage and fight bone pain.

I am only concidering Xofigo against bone pain fully aware that during this treatment the systemic cancer will live on.

All of these is my private opinion and I am not a doctor. I would feel very uncomfortable to stay 6 months without system therapy just because I am on Xofigo. Xofigo is only local treatment for bones and it doesn't treat the sistemic cancer disease. Yes, it can extend life for couple of months under certain circumstances but it could also shorten it if you are late in your cancer. Therefore I hope you have a good medical team of MO RO etc and they will make a proper decision for you.

[Islandboy2021 in reply to Seasid]

This good information.

I will continue with zoladex and would like to add enzalutamide during the 6 months of Xofigo. I would like to continue treating the cancer as well but I have been advised by the oncologist that enzalutamide is not SOC.

So I do the Xofigo and the cancer continues to spread. The Xofigo only treats the metastatic spots I currently have.

I am trying to understand.

I believe that I will have to go onto chemotherapy once I have completed the Xofigo. Can I take the enzalutamide during chemotherapy.

Thanks

[Seasid in reply to Islandboy2021]

I was told all of these. You should have a team of doctors to decide all of this.

I can't advise you. I am simply not qualified nor I can decide. I believe they are still learning and experimenting with people. Yes enza is not a standard of care. Peter Mac didn't recommend Enzalutamide to one Australian I know. I think they said to keep it in reserve, but he had Jevtana just before.

You really need good doctors to make a decision. It is not simple.

[RyderLake2]

Hello,

We have gone back and forth a few times in the past. You sound like you have a good plan. I have been on Xtandi for five years from 2017 to 2022. My PSA was steadily rising so last October I switched from Xtandi to Zytiga (abiraterone) and Prednisone. I was told in Canada your Medical Services Plan (MSP) or Pharmacare (or both) doesn't normally allow you to switch from Xtandi to Zytiga or vice versa. I got around this by being on the SPLASH clinical trial. I suggest you check to see whether you are covered.

Secondly, because my PCa has metastasized to my bones my family doctor gives me a 60 mg Prolia injection every six months. Prolia and Xgeva are both brand names for the same drug denosumab. Both are injectable preparations and both are made by Amgen. The main difference is in the dosage. Tall Allen is correct. Xgeva is normally given as a 120 mg injection once every four weeks with additional 120 mg doses given on days 8 and 15 of the first month of therapy. Taking Xgeva every three months is not the norm.

Finally have you considered Lutetium as an alternative to Radium 223? I would definitely be interested in knowing why you decided to go this route. There are a couple of BC Cancer Agency (BCCA) clinical trials opening up involving Lutetium. Good luck!

[nobaday in reply to RyderLake2]

’ Tgere are a couple of BC CANCER TLtrials opening up involving Lutetium’

NOT to my knowledge?! I got on the PR21 clinical trial but that opened in like June 2021 . It compare 6 doses of Lu177 to chemo. I did 5 out of 6 infusions of Lu177 and then had progression of tumour at C2 and less important growth of a tumour in my prostate. Tumours at T8 to T12 diminished in size/ stable.

Not sure what new trials you are referring to… SPLASH but again that’s not new?!

[Islandboy2021 in reply to nobaday]

How did you manage the Lu 177 treatments.

Didn’t you have your prostate radiated at some point.

[Islandboy2021 in reply to RyderLake2]

I have failed the abiraterone and the oncologist did not offer to switch to Xtandi. I will have to push for this. I only have remote appointments and find I am always playing catch up with the oncologist.

The bone specialist had to prescribe the Xgeva and Estrogel because this is not part of the cancer treatment. I had to get these covered by my extended medical. I will get another appointment and push for the monthly injections.

So I had three options to consider for treatment.

1. Chemotherapy, again.

2. Radium 223

3. Clinical Trial for Lu 177.

To be honest I picked the Radium 223 because it has the least side effects. I was planning on having some QOL this summer. I have been working full time throughout these treatments and need to take a break and enjoy while I can. Do you not think the Radium 223 will have any effect on slowing the spread of mets in my bones. Apparently I am lucky because the cancer is only in the bones for now.

[RyderLake2 in reply to Islandboy2021]

Hello Islandboy,

I don't think Pluvicto (lutetium) is any better than Xofigo (radium-223). They are just different. In other words, they have different targeting abilities. Lutetium targets PSMA but not all men express the protein PSMA. If you do express PSMA, verified by a PSMA scan, then lutetium can treat both bone and soft tissue mets. Xofigo mimics calcium and calcium goes to the bones. If you only have bone mets then Xofigo might be the answer as it will target and treat those mets. I think trials have shown that it is safe to take Xofigo after Pluvicto but I am not sure about the other way around (i.e. Pluvicto after Xofigo). I know in the SPLASH clinical trial, which I am enrolled in, prior treatment with systemic radionuclides such as Xofigo (radium-223) is an exclusion criteria. Lots to think about! Good luck!

[Mw921000000]

my dad is in a very similar situation. Recently became castrate resistant in September of last year. Was switched off of Zytiga and lupron to lupron and xtandi. He does not respond to lupron by itself. Xtandi is working currently. Hoping it lasts for quite a bit but am always looking for what drugs might be next. Please keep us updated with your current treatment plan. Hang in there!

[MateoBeach]

Would also favor doing the Xgeva monthly while getting the Xofigo to maximize synergy. Then you can switch to every three months. Abiraterone is no longer working for you (resistant) so certainly switching for Xtandi worth trying next. Best of luck to you.