Hi all - my husband was diagnosed in May of 2020 with PSA 290, Gleason 9, extensive bone mets, and pain the only symptom. Started Lupron and Zytega, got PSA down to 0.2 in June of 2021, did radiation just to the prostate, and everything was good until November of 2021 when the PSA started doubling every 3 weeks and bone pain increased. By February, scans were showing bone mets increasing everywhere. In March, radiation was done to the sacrum where growing mets were interfering with nerves. We entered CAR-T PSMA trial at MSK in July, and although he made it through with zero toxicity and a strong immune response, the mets continued to grow, pain increased, and he had to stop the trial in October after treating some troublesome mets with radiation to prevent nerve damage. Started docataxel in November and is half way through. Assuming chemo works to beat this thing back, can we now try Xtandi, and has anyone had success going back on Xtandi after Zytega failed (with chemo in between)? Thanks for any insight.
Xtandi after Zytega and then chemo - Advanced Prostate...
Xtandi after Zytega and then chemo
You could try that. The chemo may have reduced the amount of resistant cells. Or start with Pluvicto.
I think it's a good idea to try Zytiga. A recent trial found that Xtandi+chemo was effective even after Xtandi failed:
prostatecancer.news/2022/10...
Is Xofigo possible?
He did Zytega already but has never done Xtandi. Do you think there’s a better chance of a second try at Zytega working, or trying Xtandi for the first time after chemo?
He has no markers for Keytruda, but I guess we could do a liquid biopsy and see if the cancer has developed any helpful mutations?
I'd go for the one he hasn't tried.
Hi, may I ask if you should quit zytiga during chemo, and then swap to xtandi? Or should you keep taking zytiga during chemo, and the do the swap without any break in between?
you’ll have to ask the MO, but I would think you have to stop the Zytiga. We stopped it because he was doing a CAR-T cell trial and needed to be off it for that. We only started chemo once there was a subpar response to the trial.
There's nothing in your profile, so I have no idea what your situation is.
Yes, I just joined the forum, sorry! Here is the short version: My dad was diagnosed with PC april 2022. PSA 350, mets in bones (spine, pelvis, ribs) and lymph nodes. He startet triple therapy, with Zoladex, Zytiga and Docetaxel. It worked ok, PSA nadir in september 1,9. However, in november PSA crept up to 3, in December it was 6 and now it is 11. My dad is also experiencing increasing back pain, and CT/ MR shows rapid growth in tumors. Otherwise no PC activity in other orgsns and bloodwork good (except some fluctuations in the crp, but nothing too alarming). Now our MO had changed from prednison to dexamethasone, and my dad is scheduled to start Jevtana treatment next week. We have been considering Lu-177 prior to Jevtana, but that would have to be paid out of pocket, because it had not been established as SOC in Norway yet. We can get it in Finland, but for it to be covered by the govetnment we have to try Jevtana first. I would prefere trying Lu-177 first, but I don’t know how important the sequencing is here. Any thoughts on this? And also with regards to my first question regarding continuation of Zytiga during Jevtana? Your input is MUCH appreciated!
If Zytiga has stopped working, Xtandi may work, at least for a little while. And Chemo may keep it working longer than it otherwise would. A recent clinical trial found that the triplet of Chemo+Xtandi+ADT works better than chemo+ADT even after Xtandi has failed.
prostatecancer.news/2022/10...
Also, consider combining chemo with Xofigo, which I think is available in Norway. See the section on combining it with chemotherapy:
prostatecancer.news/2021/02...
Thank you so much! But do the Xtandi+chemo advise apply for cabacitaxel as well as docetaxel? And are there any indications of that regimen being more effective than doing the swap from zytiga to xtandi after chemo? He has already been through 6 cycles of docetaxel, so cabazitaxel is what he is scheduled for next. Any insights with regards to the sequencing of cabacitaxel / lu-177? I will ask our MO about the possibility of adding Xofigo to chemo. But I thought that might have some adverse effects with regards to the affected lymph nodes? I might have gotten this wrong, though.
I'd guess it applies to any taxane chemo, but I don't know for sure.
Xofigo won't affect lymph nodes, only bone metastases.
Pluvicto is preferred over Jevtana, but you said you can't get Pluvicto.
Thank you so much! Well, it isn’t funded. But we opted for treatment in Finland, and he is scheduled to start lu-177 early February. He had one infusion with Jevtana this week, because we didnt have the results of the psma pet-scans yet, and our MO didn’t want to waste any time. But now we got the scan results and he seems to be a very good candidate for lu-177 treatment. SUV values ranging from 13-50 in basically all mets. So both our MO and the doctors in Finland advise us to swap to lutetium treatment. We will keep the cabazitaxel up our sleeve for later. At that point we can also try recharging with Xtandi (we now quit Abi, on advise of our MO. It clearly doesnt work). I hope we have made the right call!
Great article TA. Thanks for posting.
Also your suggestion to marchinda seems very sound... to this layman anyway.😊
It may work. Some cancers resensitize to anti androgens after chemo.
If he has painful mets he could qualify for Xofigo which he could start even during chemo.
Try to get a liquid biopsy or a direct biopsy to do genomic and IHC studies of the cancer. The cancer may respond to olaparib, keytruda or cabazitaxel plus carboplatin or similar drugs.
Lu 177 PSMA treatment could be another option if the cancer expresses enough PSMA and there ae not discordant areas of cancer without PSMA expression. He would need a PSMA PET/CT and a FDG PET/CT.
He’s had tons of PSMA pet scans because of the CAR-T trial he was in. He has a lot of PSMA expression, but not all the mets have it. He has a few areas that really aggressively grew during the trial that did not light up on the PSMA scan.
The MO definitely has her eye on Lu177. We will see what the next step is. Considering the AMG 509? trial at MSK as well.
If he has discordant PSMA cancer, Lu 177 PSMA may not be indicated. They did not treat patients in that situation in the TheraP trial
thelancet.com/journals/lanc...
Genetic and IHC studies may give you a idea of what meds and trials to look for. Perhaps the PROTAC trials could be something to consider
biochempeg.com/article/282....
If I could I would consult with Dr. Aggarwal at UCSF and with Dr Beltran at the Dana Farber in Boston
Last night I watched a video,Dr Kwon was talking about zapping the mets that didnt respond to Lu177 in his patients
IMRT and SBRT has mostly worked very well for me. "Zapping Mets" is a bit controversial as a big picture treatment. The jury is out. But it does make the mets go away which is important because they get bigger and can cause serious problems. Treating spots with radiation is normally done when the spots can be counted on one hand. Or if there's a dangerous one.
I'm doing chemo plus Xtandi after both Zytiga and Xtandi stopped working. I'd say that I've had limited success. Adding Xtandi to chemo has given me more pain relief and stalled my PSA increases. But I'm doubtful that it's working very well though since my scans are looking worse and while my pain goes down for a while, it does return before the next chemo cycle. This will be my last chemo before Pluvicto. I was just hoping to slow down the cancer and I think it has. All in all, chemo and Xtandi has probably given me an extra 3 months.
There's also Cabazataxal in your toolbox for later.
hi, my dad is in this same situation and we are starting chemo for the first time next week. He is metastatic Gleason 9, castrate resistant. How is your husband doing? I hope all is well. He is also getting treated by Dr.Slovin at MSK.
Xtandi failed 
Xtandi causing pain?
Is Xtandi Failing?
Berberine and Xtandi
Off clinical trial, on to radiation and chemo
