PARP inhibitors - which one?

[HopingForTheBest1]

There are at least 5 different PARP inhibitors all currently in trials for prostate cancer treatment, including Olaparib, Rucaparib, Talazoparib etc. I am BRCA2 positive, and fully expect to be on one of these in the near future. My MO is considering Olaparib as it has the most amount of research out there and has been around the longest. How can we determine the right one for me?

I had hoped to find out from my Foundation Medicine genetic test results which I expect next week. Unfortunately, I don't think anyone knows. I had a recent meeting with a top BRCA2 researcher, who confirmed it is just too early in the clinical trial process to know.

I understand I would need to qualify for the particular trial in order to have access to the medication.

[Tall_Allen]

There's a list of them in this article. Maybe you'll be able to find one nearby, especially if it combines a PARP inhibitor with another medicine that you could not otherwise get.:

pcnrv.blogspot.com/2018/02/...

[HopingForTheBest1 in reply to Tall_Allen]

For me it is not just finding a PARP trial, it is finding the most "effective" one. It is confusing, and I don't expect anyone has an answer.

[Tall_Allen in reply to HopingForTheBest1]

No - there aren't any comparative studies yet that I know of. Most of the big pharmaceutical mfrs have a pony in the race.

[Hazard]

I don't think that anyone knows which is best PARP inhibitor for you. My somatic DNA has bi-allele deletion of BRCA2 gene, and MO told me that I was a perfect candidate for PARP inhibitors - she said I could expect a better response than other men on the trial, most of whom had a single-gene mutation.

So after 2 months on Niraparib, PSA went from 60 to 433, with significant progression of disease in bones, liver and peritoneum. So the real issue is not which one is best, but will it work at all?

My experience shows me that just because something has worked for someone else, this has no bearing on whether it works for you. But we still need to try all these things, cause the alternatives are not great.

[HopingForTheBest1 in reply to Hazard]

Were you on Niraparib with another med? Is it possible for you to try a different PARP inhibitor?

[Hazard in reply to HopingForTheBest1]

The trial I was on (Galahad trial) was investigating niraparib effectiveness against PCa. Nothing else added to the mix (I am aware of other trials which combine PARP inhibitors with immunology agents but not in Australia AFAIK.). So from a trial point if view, no I can't try anything else. There may be one or 2 PARP inhibitors approved for use in Australia (oliparib I think) but only for breast or ovarian cancer. I cant imagine my doctor prescribing it off label, nor do I imagine that I could afford it.

Here is an excerpt from Wikipedia

"A 2012 study in a cell line found that PARP inhibitors exhibit cytotoxic effects not based solely on their enzymatic inhibition of PARP, but by their trapping of PARP on damaged DNA, and the strength of this trapping activity was ordered niraparib >> olaparib >> velipatib."

So based on this, if niraparib is not working there seems little point in trying another (weaker) PARP inhibitor.

[Drcrunch in reply to Hazard]

Did you get Germ line testing?

[Hazard in reply to Drcrunch]

Yep, germ line testing was done and no genetic anomalies associated with cancer were detected. It was the somatic DNA tests which got my MO excited.

[tallguy2]

I too may shortly be faced with joining a clinical trial that combines abiraterone with a PARP inhibitor. But which one? No easy answers! Please keep posting as you move forward.

[HopingForTheBest1 in reply to tallguy2]

Will do.

[vandy69]

While being treated by Dr. Charles "Snuffy" Myers and after a Guardant360 liquid biopsy confirmed an ATM defect, he prescribed Lynparza, one of the PARP inhibitors. This was back in early 2017. I got about 9 months before PSA began to rise again and I moved on to chemo. No real side effects from Lynparza and expensive cost covered by Humana Rx plan at catastrophic level with 5% copay of $12,000/month drug.

Best wishes. Never Give In.

Mark, Atlanta

[Hidden in reply to vandy69]

Are you still on the Xtandi rechallenge? If not, how long did that last for you? I saw your post about rechallenging Xtandi and I'm curious how it worked. I've discussed rechallenging Zytiga some day, possibly after chemo, but my doctor said he wouldn't do it. Just want to see some "real world" cases.

[vandy69 in reply to Hidden]

Hi Gregg,

After my first 6 cycles of chemo with Docetaxel/Carboplatin my PSA got down to .4 from 10 at start. Rise immediately to 1.3, so we rechallenged with Xtandi which brought PSA down to .7 for about 4-5 months. Worth the try if your drug plan will approve it! Now doing chemo a second time without the best results.

Best wishes. Never Give In.

Mark, Atlanta

[Hidden in reply to vandy69]

Thanks. Looks like I'd have to go outside of the VA to do it if I ever get to that point.

[COOP8]

I don’t have any recommendations for you, but my husband is BRCA2+, somatic only, no germline mutation. He responded initially to Docetaxel plus Carbo Platin. About 7 months post chemo his PSA began rising. Switched from Lupron to Zoladex, hoping the lupron was simply not keeping his testosterone in check. PSA kept rising so started Zytiga + prednisone. No response. He enrolled in a study through our oncologist associated with Fred Hutchinson research center starting with 4 rounds of Docetaxel/Carbo Platin, followed by Rubraca (Rucaparib). So far he has responded well to both the chemo and Rubraca. Last PSA was 3.79, down from over 200 last spring while on Zytiga. Did you do the Foundation Genetic testing in addition to previous genetic testing? If so, what additional info does it give you?

[HopingForTheBest1 in reply to COOP8]

MSS, PTEN loss, low tumor burden, TMPRSS2

[PCASURVIVOR]

I was diagnosed with G9 November of '21. PSMA showed no mets, but tumors were judged aggressive. I entered clinical trial of Niraparib, Zytiga/prednisone and Lupron for 6 months with SBRT at the mid point of drug treatment. I had significant gastric effects from PARP so MO directed me to stop Niraparib at the end of 4th month. PSA is undetectable. Negative gastric effects have abated and I have regained some of my very significant weight loss. I would do same treatment again if needed as I believe PARP is very effective against soft tumors. I had multiple genetic tests none of which indicated any specific expressions like BRCA2 and others. IMO, PARPS are a substantial step forward in PCa treatment and I hope my participation in the trial is of benefit to my sons and grandsons. Best of luck my friend, I will be in prayer for you and others.

[HopingForTheBest1 in reply to PCASURVIVOR]

Thanks for your post and prayers. After being on Olaparib PARP for 2 years, I recently had a Guardant liquid biopsy. It identified that my BRCA2 mutation has become a "reversion" mutation, which means that PARPs will no longer be an effective treatment for me. A reversion mutation restores the ability of the gene to produce a functional protein.

[HopingForTheBest1]

Nothing, other than no future treatments targeting BRCA2 specifically.