Options after Zytiga fails

[davebliz]

I've been on the Magnitude clinical trial for 8 months and now Zytiga has failed. I have extensive bone mets (greater than 30). The most recent bone scan shows 5 new mets so I'll be off the trial. I'm in Canada and think my next options are either Radium 223 or chemo. I've had genetic testing and BRAC 2. If I go with Radium 223 (complete the 6 sessions) can I do Radium 223 later, ie a year later? Thanks.

[Hidden]

If you are BRCA2, you could take a PARP inhibitor such as Olaparib or if you go with chemotherapy add Carboplatin to a Taxane (either first-line Docetaxel or second-line Cabazitaxel).

I discussed this with my doctor and he said he would try the PARP inhibitor first. I would put off Radium 223 until I went through the other treatments. That's what I would do, but talk to your doctor about it.

[davebliz in reply to Hidden]

In the clinical trial I was on, it was blind so I'm not sure I got a PARP or a placebo. Hoping I can find this out.

[MateoBeach in reply to davebliz]

When you are officially out of the trial, they should inform you what you received so you can plan best how to move forward. Unethical not to.

[HopefulSis in reply to davebliz]

Yes they will “unblind” you in the trial and you’ll know if you received PARP or placebo

[Magnus1964]

Doing xofigo next would give you a break from hormone therapy. You could then move on to xtandi.

[davebliz in reply to Magnus1964]

Thanks, Wouldn't I continue on with Zytiga when I did the Xofigo?

[Magnus1964 in reply to davebliz]

I don't think so, not if zytiga is failing. You could do casodex with xofigo and xtandi for later.

[RyderLake2]

Hello, I am not sure where in Canada you live but there are several clinical trials of Lutetium 177 recruiting around the country. I know for certain that the British Columbia Cancer Agency (BCCA) is hosting one. There are probably a few more in large centres in Alberta, Ontario, Quebec and elsewhere. Good luck!

[davebliz in reply to RyderLake2]

Thanks. I'm in BC and see there is a clinical trial in Vancouver of LU -177 versus chemo. I'm near Victoria so this would only be good if I got assigned to the LU - 177 arm of the study.

[RyderLake2 in reply to davebliz]

Hello, I am in BC too. I think that the Lutetium clinical trial might be worth investigating. If nothing else, the folks at the BC Cancer Agency (BCCA) will give you a PET scan which is far more precise than MRIs and CT scans. This scan is difficult to get in BC. My advice, for what it is worth, is to do Lutetium 177 before Radium 223. I think I read somewhere that if you have been treated with Radium 223 then you are not eligible for Lutetium. Check with your medical oncologist or the BCCA folks hosting this trial. Hope that helps!

[davebliz in reply to RyderLake2]

Hi. Where in BC are you, I'm actually on Salt Spring Island. I've actually already had a PET scan (Dec, 2020) in Vancouver as part of another study. I'm not sure of the actual results except the oncologist said 'there were too numerous to count mets". I looked at the clinical trial on Lu - 177 and I didn't see an exclusion for previous Radium 223. Do you have a reference? thanks.

[RyderLake2 in reply to davebliz]

Hello, I live in Chilliwack. My wife and I lived in a rural upland area of Chilliwack called Ryder Lake for 30 years (hence the user name). We just recently moved to a gated community on the valley floor so are no longer hillbillies! I have been battling Stage 4 metastatic prostate cancer for over eight years. Diagnosed on May 30th, 2013. My Initial PSA was just below 1700 with extensive bone mets but fortunately no soft tissue involvement. It has been quite the journey but my cancer seems to be responding well to Zoladex (from diagnosis) and Xtandi (for nearly four years). It seems your situation is similar to mine so stay in touch.

[Tall_Allen]

Yes, you can re-do Ra223:

onlinelibrary.wiley.com/doi...

You have several good options that I can see:

(1) Combine Xofigo with a PARP inhibitor. Read the section entitled "PARP inhibitors." I believe the combination is synergistic for men who are BRCA+.

prostatecancer.news/2021/02...

There are a couple of open clinical trials in the US, which probably accept Canadians:

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

You can also do them sequentially without a clinical trial.

(2) Combine Xofigo with docetaxel+carboplatin. Read the section entitled "Chemotherapy" in the Xofigo 2.0 article. They can reduce the docetaxel dose in the combination. I suggest adding carboplatin because patients who respond well to PARP inhibitors usually respond well to docetaxel+carboplatin.

You can also do them sequentially.

(3) PARP inhibitor before or after docetaxel+carboplatin. They do not seem to be cross-resistant and when one works well, the other works well too. PARP inhibitors often are toxic, so they may not combine well with chemo.

(4) Combine Xofigo with immunotherapy. Another synergistic combination. There is this clinical trial:

clinicaltrials.gov/ct2/show...

(5) Th-227-PSMA. Th-227 becomes Ra-223 and detaches from the ligand, so you get two therapies in one. Described here:

prostatecancer.news/2018/10...

The clinical trial has been expanding to several new locations, so I assume it is going well. They require that you do at least one chemo first:

clinicaltrials.gov/ct2/show...

[davebliz in reply to Tall_Allen]

Thanks TA, lots of possible options. Will be interesting when I talk with my oncologist.

[MateoBeach]

Ah! When am I going to be able to visit Victoria and Vancouver Island again? Alas the Blackball Ferry is still not running. Best of luck with your treatment choices as TA has laid out the options well.