PARP inhibitor Olaparib, phase 3 study findings (PROpel)

[Maxone73]

While we wait for the next generation PARP inhibitors to become available (I have written about it few weeks ago and I will soon have some first hand data), here are the results of Olaparib +Abiraterone

It actually has decent effect also for people with no HRR mutations, but it works at its best with BRCA mutants.

urotoday.com/recent-abstrac...

[KocoPr]

OS for mCRPC was 42 months olaparib +aberaterone vs 37 months placebo arm.

[Maxone73 in reply to KocoPr]

for non mutants, yes

[Proflac]

Thanks. Is it a difficult tx to tolerate?

[Maxone73 in reply to Proflac]

Check Coolone’s answer, it’s first hand!

[Cooolone]

Olaparib has some high toxicity for some patients! Average time to experiencing SE's is approx 16 months, many patients having to stop using it. Mainly it attacks the marrow and lowers the body's red & white blood cells...

I've been on it, since January 2023, my blood very early on exhibited signs of anemia, but borderline actionable (just at the lowest of normal) and has stabilized there. Recent drop with white cells even further causing concern and weekly blood draws. With Olaparib you get monthly blood draws to monitor for these toxicities, so intervention can occur ASAP if needed.

I get Degarelix, and Darolutamide in addition to the Olaparib. So far, so good! Olaparib due to BRCA 1 & 2 deletion with stageIV met tissue genomic testing identifying approx 11 markers, with 3 being actionable with drugs. 2 approved and 1 investigatory (Trial). We shall see... Issue with Olaparib is nobody knows the long term use issues as it hasn't been around long. I hope my body tolerates it for a very very long time and my PCa doesn't learn how to become Resistant!

Best Regards

[Maxone73 in reply to Cooolone]

Thanks for the insight! I hope to have something to add soon some great news about a new way more precise parp1 inhibitor from AstraZ which seems way more selective

[Cooolone in reply to Maxone73]

I've read about it, is interesting and keeping an eye on it. The PARP inhibitors have their place, like Check Point Inhibitors as well... What's more important than the drugs themselves is the progress being made identifying patient biomarkers and who would benefit best from what drug regimens. Is interesting times for sure! Many many avenues to try and keep track of, too many some times, and that IMO is a good thing!

All the Best!

[Proflac in reply to Cooolone]

Thanks for the update on your experience and good luck going forward.

[Chris52981 in reply to Cooolone]

my dad is just going on this due to some changes in measurable disease and psa increase- he was on xtandi- he has a somatic BRCA mutation- how well are you tolerating this and can you still have a good quality of life?

[dhccpa]

What are HRR mutations? Or is that in the article? I'll take a look.

[Maxone73 in reply to dhccpa]

Homologous Recombination repair Repair genes (like BRCA1, BRCA2, PALB2, ATM, ATR, CHEK2, FANCA, MLH1, MRE11A, NBN, RAD51C, CDK12)...like my bastard ATM, they bring no good news and (on average) shorten your life when you have PCa

[dhccpa in reply to Maxone73]

Yes thanks. I'm very weak on gene knowledge.

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

I'm very weak on all knowledge.

Good Luck, Good Health and Good Humor.

j-o-h-n

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

All is worse than general.

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

Is that all?

Good Luck, Good Health and Good Humor.

j-o-h-n

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

Not sure. Outside my sphere...

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

By all means, that's getting around it....

Good Luck, Good Health and Good Humor.

j-o-h-n

[Juju0713]

Does this study include patients who have progressed on a previous NHA such as xtandi?

[Maxone73]

Nope, no prior NHA

[Juju0713]

Thank you. My dad is currently taking lynparza after progressing on xtandi and I have wondered if it would do any good for them to also add on abiraterone as well but wasn't sure due to cross-resistance and haven't really been able to find the answer to that