Immunotherapy Clinical Trial or Olaparib (Lynparza)?

[PCdaughte]

My dad was diagnosed with Advanced PC in summer 2020. Gleason score of 9/10. PSA of 71. Since then, it's been one dose of bad news after another: Prostatectomy didn't bring his PSA numbers down. Bone mets on spine, pelvis, possibly liver. Castration-resistant. BRCA gene present.

He did radiology on his spine and pelvis mets in April, but it was clear that it was only for pain relief, not treatment.

After only 6-months on Abiriterone (Zytiga), his PSA is now back up to 700.

We've been offered two options:

1. a trial of atezolizumab + cabozantinib - an immunotherapy treatment that seems to be promising in Breast Cancer. But, if he is put into the control group, he'd receive enzalutamide (another ADT drug).

2. Olaparib (Lynparza) - I'm not super convinced of the efficacy of this treatment course. It looks promising in those with the BRCA mutation, but only against a second ADT drug (the UK hasn't approved it as a treatment because of this).

I'm leaning toward the trial, since Lynparza only showed a median of 5 months more progression-free survival vs moving to a second ADT drug.

Any thoughts on trial vs Lynparza. Or is there something else we should try? I've read some studies that showed antiandrogen withdrawal syndrome is positive in men with higher PSA numbers.

I'd appreciate any feedback as I'm researching as best I can, but there's so many ways PCa can present differently and I'm a bit lost.

Thank you.

[Tall_Allen]

Lynparza, of course. Why would you not go with the sure thing?

prostatecancer.news/2019/10...

The side effects can be rough, though.

Cabozantanib + atezolizumab had decent results in the Phase 2 trial, but the side effects were onerous as well:

meetinglibrary.asco.org/rec...

In that trial, they only looked at tumor response, not at overall survival. I confess I'm jaded by cabozantanib. It has failed as a monotherapy to extend survival in all previous trials. It changes the tumor microenvironment, making metastases harder to detect. This may have simply masked the tumors and not provided a real survival benefit.

[PCdaughte in reply to Tall_Allen]

I am concerned about the side effects, but like you said, both look to have fairly onerous side effects. He just feels so miserable on the Zytiga that I hate knowing that he's unlikely to get the relief he's hoping for on another treatment.

Thank you for the links and the info. I just want him to be able to make an informed decision about his next steps and these will help.

[Tall_Allen in reply to PCdaughte]

It sucks that the treatments that work the best also have high risk of side effects. Of course, the BRCA2 mutation is what made his prostate cancer so aggressive. But, so far, it's one of very few genomic mutations that have a treatment.

[PCdaughte]

Thank you for the response. He isn't sure which he has BRCA 1 or 2 . We're meeting with his doctor tomorrow, so I'll confirm which one and whether they did a complete gene mapping.

[Hidden in reply to PCdaughte]

He's likely to be BRCA2. BRCA1 is not that common in PCa. Germline BRCA1 in prostate cancer patients is .44%.

[ScottfromSD]

Hi. I’ve been on the cosmic-021 trial (Cabo + Atezo) for the past 12 months. The side effects of the Cabo (nausea and diarrhea got pretty brutal) but became more manageable with a dose reduction. It does require a time commitment in that you will get Atezo infusions every 3 weeks - I’m on number 18. Understand that this trial is judged by scans, not psa. The psa will likely rise and this is disconcerting, regardless of what the scans say.

If it were me, and I don’t have the brca mutation, I would probably try olaparib first and then move to the trial if necessary.

[PCdaughte in reply to ScottfromSD]

Hi Scott,

Is there any reason why you'd try olaparib first before moving to the trial? It sounds like, despite the side effects, that Cabo + Atezo is working well for you.

[davebliz]

Hi, I was not aware that there was a difference for treatment or response between BRCA1 and BRCA2. Do you have more information? Thanks.

[Concerned-wife]

urotoday.com/conference-hig... In case you haven’t read this.

[PCdaughte in reply to Concerned-wife]

Thank you, Concerned! This is a wonderful resource to be able to show my family! They had concerns about the ~5 mo. median progression-free survival time, but this clearly shows a better benefit for those with a BRCA mutation.

[Balsam01 in reply to Concerned-wife]

Concerned, I could not get this link to work. Could you re-send it or something? Thanks.

[PCdaughte in reply to Balsam01]

Balsam, when it redirects you, it adds "Posted" at the end. Try this link:

urotoday.com/conference-hig...

If it doesn't work, try copying and pasting the link from the redirect page, substracting any text after ".html".

[Balsam01 in reply to PCdaughte]

It worked! thank you very much!

[Concerned-wife in reply to Balsam01]

sorry didn't work for me either. trying to send a different way. you might need to copy and paste.

urotoday.com/conference-hig...

[Concerned-wife in reply to Balsam01]

sorry, didn't work for me either. trying a different way urotoday.com/conference-hig...

[HopingForTheBest1]

I am BRCA2+ and Gleason 10. Had Olaparib before it was approved, via off-label use. It was effective for close to 2 years, keeping my PSA undetectable until it ran its course. My side effects included anemia, a partial blood clot resolved by Eliquis, fatigue and muscle weakness. Olaparib is the way to go for those of us with BRCA mutation.

[PCdaughte in reply to HopingForTheBest1]

Thank you, Hoping! I have seen some of your posts as I was searching for information on Olaparib, and your experience and other replies has me leaning toward recommending it.

[ScottfromSD]

Hopefully Olaparib will knock back the cancer, which appears to be moving very aggressively if the psa is at 700. The trial is … a trial so I would go with the proven. The trial also will not lower psa which is hard to deal with when you have a quickly rising PSA. From what I’ve been told, you should know within 6 weeks or so if the Olaparib is working. If not, move on over to the trial.

[PCdaughte in reply to ScottfromSD]

Yeah, it does seem to be a particularly aggressive case. I agree with you on going with a proven drug, but I guess there is always the temptation to go with a trial and hope it's a "miracle drug". But given that it's been used in Breast Cancer, I know that it's not likely.

I'll ask tomorrow if it might be possible to move to the trial after trying Olaparib.

[Hidden]

We tried the Olaparib for three months. Totally wiped out his ability to do almost anything. He lost 30 pounds in three months. Threw his mind into dementia. He couldn’t differentiate between a phone call, a text, an email. He couldn’t take his medication without help. He never knew what day it was. He couldn’t watch TV because he couldn’t follow a storyline. It was brutal. And from my research over half the people on that drug have similar reactions. I’m not saying your dad will. Just that it’s possible. So keep an eye out. I wish we’d gone to Jevtana. They say the side effects are less than Taxotere. And he handled that fairly well. There are worse things than chemo out there.

[PCdaughte in reply to Hidden]

Thank you for the perspective. This is a major concern since he is still working, so I'll keep an eye on it (and suggest that he move in with one of us kids, if necessary).

[Curehunter]

I'm also in the UK and currently on Rucaparib (another Parp Inhibitor) as am also BRAC2 . Worked well for 5 months and side effects all manageable.

[j-o-h-n]

So tell us how old is your dear Dad? Thank you...

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 05/18/2021 5:55 PM DST

[PCdaughte in reply to j-o-h-n]

He is 64.

[j-o-h-n]

A young chap..... Thank you... You're a wonderful daughte....Give him my regards and Kiss and Hug him.... and make him laugh....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 05/18/2021 6:21 PM DST

[Mollygrace666]

was Docetaxel ever mentioned ???......working pretty well for me