Decision time. My husband has not had success with any of the standard of care treatments, docetaxel, twice, zytiga, xrtandi, radium 223 and cabazaiaxel .He has a rising PSA currently of 178 and is faced with a decision of continuing to qualify for the AC225 clinical trial( his blood levels are there yet) or trying a parp inhibitor Oliparib . However since he does not have the BRCA gene we are worried that it will be another failed attempt. Any suggestions or recommendation would be greatly appreciated . We are both done with this nightmare but will not give up the fight. Thank you
Oliparib without the BRCA gene - Advanced Prostate...
Oliparib without the BRCA gene
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joann48
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Olaparib not effective without Brca 1 or Brca 2 mutant.
I would go with the AC-225 trial or take a look at the Arvinas trial for ARV-110 trial--the androgen receptor degrader for MCRPC....good luck to you both....
Don Pescado
I've heard from patients that PARP inhibitors can have significant side effects.
I am getting a grade 3 fatigue fr0m olaparib six months out. No other SE’s, but this fatigue is rough.
Yep. I had severe constipation and needed an enema to cure it.
Yes. For me, SE have been serious anaemia, fatigue and constipation
No side effects for me (yet), 4 months on trial.
Do you haveinfo on ARV-110 It is being recommended by several members. thank you
I think it sounds interesting and am hopeful about it. One of the several pathways of castration resistance is that the androgen receptor (AR) multiplies - this was developed to de-escalate it. They also hope it degrades the mutations that make the AR resistant to Zytiga and Xtandi.
It may work in patients with somatic BRCA mutations. It is less efective with other mutations.
Joann48, Sorry the SOC treatments have not helped. PARP inhibitors have worked on men without the loss of BRCA1/2. There are a number of other genes that could be effected. BRCA mutated genes are the most studied but PALB2 and FANCA genes are also targets. There are more, look up the TRITON 2 poster from ESMO this year. Have you had a genetic work up and what other markers did it flag? Were the tests carried out on the cancer cells AND the blood.?
Joann48, From the little I know about the DNA repair function, there is a cascade of genes that spring into action when a double break occurs. BRCA1, PALB2, BRCA2, RAD51....etc. The scientists are still putting that puzzle together. But they tested men and SOME responded without a BRCA 1/2 loss. There are attempts to generate a BRCAness by using drugs called 6TG that are approved for some blood cancers. I would check carefully to see if any of the 5 PARPi companies are recruiting outside of the BRCA genes. If you take one PARPi drug it will probably exclude you from the others so choose carefully. Good luck.
Joann48, Was the RAD51 loss from a blood test or from cells taken from a site in the body?
biopsy of adrenal gland that has metastasized. Do you know anything about keytruda?
Joann48, Keytruda is a form of immunotherapy that requires a target in prostate cancer. This is checked during your genetic work up. It will be reported as a MSH loss or a high tumor burden. Your doctor can better inform you of this from your report. Like all treatments whether Keytruda or PARPi, how you respond is unique to you so don’t lose hope.
It isn't clear to me what the requirements of the trial are, but why not go to Germany and try lu177 PSMA or actinium 225 PSMA on your terms, not those of a trial.
Hi Joann48, sorry to hear about your husband..sounds like your husband and mine are in the same place as to
Out of most options. Long journey and many bumps in the road.... We have chosen to go with Lu - 177 ?
May I ask where you live? We are in the states. I believe that if our hearts and mind are in the same place we can over come most anything!! Hang in there, never give up and never give in....
Good luck to you and your husband. Take care.
Sincerely, Lynn
Where are you getting LU-177 in the states? I thought treatment was mostly in Germany ??
Hi .... We live in the suburbs of phila.
Where are you located... They also have the Lu-177 scan and treatments at Sloan in New York.
Good luck to you... Lynn.Pa.
Hi... Chicago
We are in New York and the trial is at Weil Cornel. Jacks Blood levels see too low to qualify so we are hoping they improve. Where will you starting the trial and why did you choose Lu-177 rather than AC225
Thanks and Good luck
I second that PARPi maynot be the best choice. Ac225 is available in Germany, but also from what I've read in this forum, at lower cost from South Africa and Australia - in case your husband can tolerate the travel. The ARV-110 trial that one member mentioned is also worth looking into.
Joann48, If PARPi is not a good fit then other trials are worth a look,
ARV-110 (as mentioned earlier)
VER-111, a new form of chemo
AMG-212, bringing T-cells into play
These are all recruiting last time I checked. Your Doctors mention of hospice would make me question his commitment. Best of luck.
Thank you. I agree. About the Dr. we are switching oncologist to someone who thinks outside the box
Is he being treated by Dr Tagawa at Weill Cornell?
Sorry we never connected before moving to Cambridge. Did your husband end up using Dr Tagawa? What happened with Dr Eshaghian's protocol? Where are things at now for your husband?
Yes. Is your husband ?
I'm not a doc but I understand that if you DON'T have a mutated BRCA gene y ou won't qualify for the PARIBs as "off-label" treatment prescription??
It does seem to show some benefit if you DO have say BRCA2 mutation as I do. My MO says that is the next treatment we will try WHEN Lupron starts to fail me based on PSA.
2Dee
Has he been tested for Germline (DNA) BRCA or Somatic (cDNA)?
They are two different tests. Treated the same clinically though. My husband doesn’t have GERMLINE BRCA2 but it did show up as how his cancer mutated (Epigenetic) in the Gardant360 test which looks at DNA of circulating tumor cells rather than normal DNA.
""Do you need the BRCA gene for Keytuda ?" Your question.... I didn't forget you, but
I'm still waiting for a response from my doctor. BTW I'm being treated right across the street from Weill Cornell at Sloan Kettering.
Good Luck, Good Health and Good Humor.
j-o-h-n Friday 07/12/2019 6:32 PM DST
Are you using Michael Morris?
Yes I am.... Not only using him but also abusing him....
Good Luck, Good Health and Good Humor.
j-o-h-n Saturday 07/13/2019 11:05 AM DST
From my post to you 7 months ago:
Take the Train to New York City and see Dr. Michael Morris at MSKcc at the Kimmel Center on East 68th Street Near First Avenue. Well worth the trip.
Good Luck, Good Health and Good Humor.
j-o-h-n Wednesday 12/26/2018 8:56 PM EST
Good Luck, Good Health and Good Humor.
j-o-h-n Saturday 07/13/2019 11:11 AM DST
We have been using Dr Tagawa and just moved to Cambridge and have started at Dana Farber with Chris Sweeney. We felt good about Dr Tagawa's care.
What are your husbands other issues/symptoms beside a rising PSA? My husband's is 1188 and no one is talking about Hospice.
Sounds like from all the answers that there are many options. Problem is finding the right MO to help you find the right treatment and then the next right treatment.
I think we all know we aren't talking about a cure here. Quality for as long as possible. When quality goes out the window, time to start living your dieing. I'm not ready for that to happen for my husband either. Some days are way harder than others.
I hope you find a treatment that gives your husband time that is worth living. All the best for both of you and all of us.
Where is your husband in disease progression. Does he have bone Mets? Getting really stressed . We are waiting for lab results to see if he is eligible for AC225 clinical trial. Ugh!
Hi joann48,
I had a friend with Pca who did not respond well all standard treatments and he was Brca2 positive so docs gave a PARP inhibitor which made Psa rise from 40 to 432 in 2 months. He was also due to get Lu177 but then docs found a lot of mets in his liver which did not show up in PsMa Ga68 PET/CT scans so Lu177 would have not worked on the liver mets. He soon succumbed to overwhelming sickness and passed away at 59, leaving a beautiful wife and 2 kids behind. There can be very painful consequences for those left behind after a partner passes away, just so sad.
In your original post you said your man had had only Ra223, but that works mainly on bones where calcium is being disturbed by Pca bone mets.
The best thing now might be Lu177 which has less severe side effects than
Ac225.
I had no lasting luck with many treatments including chemo and between last November 2018 and May 2019 I had 4 shots of Lu177 and Psa fell from 25 to 1.6 about 5 weeks ago, maybe its still going lower, and last PsMa scan showed some bone mets were healing up, and no new mets, and hardly any soft tissue mets were visible. I might have mets with don't show up in the PsMa scans and they cannot be treated by Lu177 or Ac225.
Before I began Lu177 I had very good blood tests. I'm 72, and was very fit
due to cycling many km all through my treatments, about 100,000km between 2010 at earlier this year.
If your man's blood tests show he is strong enough to withstand Lu177, then go for it. PARP seems to only work if Brca1 or 2 is found and then only small success numbers, and PARP inhibitors might make things worse.
Here in Australia where I am the law says I can buy Lu177, Ac225 etc even though these things have not passed phase 3 trials, and where all other treatments such as ADT and chemo have failed.
At my 4th Lu177 treatment in Sydney there was one other Australian and two men from US who could afford to fly over here and pay usd $6,620 for each Lu177 infusion done by docs at Theranostics Australia see their page at theranostics.com.au/
Average response to Lu177 is about 14months based on trials mainly in Germany where Lu177 was developed some years ago. I suspect the 14 months was based on some very sick patients for initial trials, and I guess longer time could be expected for men with lower Psa to begin with, like myself, so I'm hoping for a longer time with a low Psa.
I was told that of patients who qualified to be treated due to PsMa scans showing their mets, success rate with Lu177 was about 70%.
My local oncologist is well pleased with my response, but he knows Pca is like a weed, you try to mow it down, put weedkiller on it, and yet it springs back up. Well, OK, but I am still here since diagnosis in 2009, when Psa was only 6, but I had a high score Gleason 9 that was inoperable. Pca had probably spread by then, but ADT worked from 2010 to 2017. Mets only showed up in 2016 when they became big enough to see in the scans.
There's a trial here in Oz with Keytruda + Lu177 which will test the idea that Lu177 makes the Pca unable to hide from Keytruda, IT.
I have heard about Provenge IT, but success is not so common but where there is success it can be very long lasting if the altered white blood cells can regenerate in future to retain the alteration that allows the immune cells to see the Pca cells as rogue cells and kill them.
We may all have good immune systems but our white cells don't recognise cancer as the enemy, but as our own OK cells, and may even protect the cancer cells from anything doctors try to do.
I am not aware of Lu177 trials in US, must be some going on. But here I can just buy it, or be in a trial, but one trial was for Lu177 or Cabazitaxel, and if you failed one you were assigned to you could not switch to the other, so I was not prepared to take a chance on the choice offered, so I just paid for the Lu177 because I had the money, and it was available in Sydney. But trials here don't cost anything. I live in Canberra, a small city, 300km south east of Sydney, and it was a nice slow trip on an old train, and Govt paid the fares. I had to travel to and from 4 times over 24 weeks. There was no way I could have afforded to stay in Sydney for that time. Specialized nuclide treatments like Lu177 will probably never be available at most hospitals.
So I had to travel to the bigger city to get the special treatment.
I wish you the best of luck.
Patrick Turner.
Thank you for your encouragement, My husband cancer has metastasized to his bones, adrenal glands and a few lymph nodes. His pain is handled by tramadol or some days Percocet. We are not ready to give up and will continue to fight. We are looking forward to working with Dr Tagawa and are hoping for more time.
Same. Bone Mets all over skeleton
Just discovered a new tumor in right adrenal since February
No pain though. Maybe an occasional twinge but Tylenol takes care of it
We thought about Dr Drake and Dr Morris
Ended up with Tagawa and now in Boston at Dana Farber with Dr Sweeney
Keep seeing new MO’s till you find your guy
It’s worth the hassle
I’m thinking about getting a second opinion from Drake myself
We all just want the best options!!!
Our husbands deserve that.
If you want to call let me know
Consults with Charles Drake at Columbia and Michael Morris at MSKCC may be beneficial. I'm just another patient--and on the west coast, but these are two top MedOncs that my California compatriots are willing to regularly travel to see. I heard them both at ASCO GU Symposium in SF this year. Impressive and very (patient perspective) open spirited (non-stuffy/authoritarian) kind of MD's. Drake especially gets "top PCa MedOnc in the country" comments from even west coast guys. New consult set-up process can be daunting, but sometimes highly productive (and yes, sometimes not.) But these two are not "go to hospice" kind of guys...
FWIW, the Hutch in Seattle has (or had?) a BAT + PARPi trial underway for non-BRCA guys. Unknown status, tough geography for you, but my (engineer) gut likes the synergy potential. Your concerns about PARPi downsides are not unfounded -- so I'm not trying to bend your thinking. Just brainstorming. You're getting good, wide ranging inputs here.
You seem to GET that the real decisions here are YOURS based on the best opinions you can find. Good work and research.
Warmest good luck.
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