Abiraterone/enzalutamide+PARP inhibitor better than abiraterone/enzalutamide alone for mCRPC, even without BRCA+

[Tall_Allen]

A new therapy may be approved next month for all men with mCRPC. Previously, PARP inhibitors were only approved for men with mutations in the BRCA gene (BRCA+) and a few other rare similar mutations. By combining the PARP inhibitor (Lynparza (olaparib) or Talzenna (talazoparib)) with either abiraterone or enzalutamide, cancer progression was slowed, even in men who were BRCA-.

My guess is that these men will probably also do well with a taxane chemo (docetaxel or cabazitaxel)+ carboplatin +abiraterone/enzalutamide.

The FDA is expected to approve the combination next month.

Here's an article describing the trials:

prostatecancer.news/2022/06...

(Update) The FDA has decided to only approve the combo in men who are BRCA+

astrazeneca.com/media-centr...

[cesces]

Nice. Thank you

[Papillon2]

Cool !

[dixiedad]

There is so much jargon/abbreviations used here that I'm often lost. I know (think) that there's a glossary (or something) of terms used here, but it's damned tedious to go back and look up everything I don't know about.

End of rant.

😣

[Tall_Allen in reply to dixiedad]

Here's a glossary:

prostatecancerinfolink.net/...

It doesn't matter if you don't know what a PARP inhibitor does (it prevents repair of DNA damage in cancer cells). It's a type of medicine used in cancer treatment - that's all you need to know.

mCRPC= metastatic castration-resistant prostate cancer

BRCA+ is one kind of genetic mutation

[dixiedad in reply to Tall_Allen]

Merci

[Cooolone]

Approval will be great for many...

I've already traveled the CHAARTED path, moving along the Magnitude and Propel paths as well. Switched from Orgovyx to Degarelix last year, and added Darolutamide which stabilized PSA back to undetectable levels. Had Whack-a-Mole Radiation therapy to address PET Imaging spots (3) recently. And now added Olaparib to the mix like a nice little cherry on top!

I think insurances will push back for a while as the nut for Lynparza is pretty high ($20K per Month +/-)... My insurance initially quoted me almost $4k copay (per month), but I was able to mitigate that. Same for the Darolutamide, pretty heavy $ depending upon insurance. Drugs I'm consuming now amount to approx $1k per day, nuts right!? Fingers crossed they work and keep working

Previously you could only get the PARP inhibitor in a CRPC environment, so it's good if they take those restraints off. I tested for a few genomic markers over 2 years ago with the discovery of mets, had the tissue tested. But because a castrate sensitive environment precluded me from their use, I had to wait for disease progression to use them. Well they got it as I progressed barely one year post Docetaxel... But it's ridiculous for the patient... When those making these decisions certainly aren't suffering from the disease, not to have access to drugs because of arbitrary restrictions! Especially when the drug is designed for a genomic marker and not the cancer itself (technically). Is a good thing the drug makers are always trying to bring drugs down the line to earlier and earlier use, via trials to demonstrate efficacy for that purpose. But if the FDA allowed their use once it's demonstrates effectiveness at all, for all spectrums of patient risk or progression, trials wouldn't be needed. Just recording of results... Just my thoughts as a "just started" user of Olaparib!

Thanks for posting!!! Is good news indeed.

[HarGreg]

Thank you for your constant contributions for PC.

[Fiddler2004]

Thank you! 🙏

[TEBozo]

Thank you Tall Allen.

[GreenStreet]

Thanks very much for the info. I guess we will struggle to get it on the NHS but useful to know of the potential benefits.

[ehoneycutt29]

Thank you my friend!

[EdBar]

I see that none in the trial were previously treated with a second line hormonal - enzi or abi. Currently a large portion of men with advanced PCa have already begun these treatments, and one must look closely at the side effects from Parp inhibitors, it’s a rough ride. It’ll definitely be a QOL decision if men are given the choice when the time comes for those still on first line treatments of whether to add just a second line hormonal or adding a Parp inhibitor to it.

Ed

[Tall_Allen in reply to EdBar]

I agree. I guess one would use whichever advanced hormonal hasn't been tried yet. The side effects seem worse than docetaxel. The QOL, as a whole, isn't affected, but that's probably the result of the improvement due to delayed progression.

[PCASURVIVOR]

I was diagnosed with PCa 12/11/21 following in bore MRI guided biopsy in November 2021. Two tumors, largest was Gleason 9 (4+5) second was Gleason 7 (3+4). Even though my PSMA/PET confirmed no involvement outside prostate, my RO suggested that I was an excellent candidate for a subgroup of the ASCLEPIuS trial. The trial regimen is 6 - 28 day continuous cycles of ADT (Zytiga 1000mg +prednisone 5+5 and lupron - 1 injection to begin cycles 1 and 4) plus Niraparib (100 mg - twice daily). I also received SBRT - 5 sessions - 39 Gy total - beginning on Day 21 of Cycle 3 and continuing thru Day 4 of Cycle 4. Niraparib SEs are typically cardiovascular or gastro - my gastro SEs were very significant - lost 30# during cycles 1&2. RO enforced Niraparib holiday the last 14 days of Cycle 4. I attempted resumption of Niraparib on day 1 of cycle 5 at 100 mg daily - terminated at Day 10 of Cycle 5 due to continuing severe gastric SEs. ADT was terminated at day 28 of cycle 6 per trial protocol. Beginning PSA was 8.6 - <0.05 by midpoint of cycle 2 and <0.05 at conclusion of cycle 6. Beginning testosterone was 440, ending testosterone was undetectable.

My PSA/Testosterone is being monitored every 3 cycles for next 2 years and annually thereafter until I reach 5 years post treatment. Monitoring results at 3 cycles post treatment was PSA - 0.07 and testosterone- 242. Results at 6 cycles post treatment was PSA - 0.08 and testosterone - 319.

I am hopeful for LT benefit from the Niraparib.

[Tall_Allen in reply to PCASURVIVOR]

The effect of so many drugs is almost always greater with earlier use and with combinations.

[HopefulSis]

I don’t comment often as I’m on this site for my brother with PCa. I am an RN in gyne oncology and would like to share that we have dozens of patients on PARPs and that they can be well tolerated. GI symptoms usually are no longer an issue beyond 4-6 months. It’s exciting to see that they may be approved for men without BRCA. We have a patient who started Olaparib on a trial and is still on it 5 years later!

[Shorter]

I have been to many cancer forums, but none where I can get the information I can get here. Thanks Allen.

Mike

[tallguy2]

thanks for posting this info!

[pilot52]

Tall Allen you are shit hot!!! Great info.....I am currently on a second regiment of repurposed Lu-177 in Delhi, Dr. Sen is very prudent about not taking you to toxicity. I will put up a summery once everything is complete. So far two infusions with good results. We are doing a scan in April to determine if a 3rd infusion is required. Again will give details later...Blue Skies Sky King and Penny..(woof)

[alephnull]

Tall, I followed you over here from that other forum, you never fail me with your research!

Thank you Sir!!

[Amberliteyears]

Tall_Allen, I have tried researching to no avail. Do you know if this has been approved yet?

[Tall_Allen in reply to Amberliteyears]

They expected approval by May

[Tall_Allen in reply to Amberliteyears]

The FDA has decided to only approve the combo for those in whom the PARP inhibitor is approved - BRCA+ only

astrazeneca.com/media-centr...

[Tall_Allen]

That is totally wrong. Another reason why youtube videos are not a good source of medical information. PARP inhibitors are very toxic. It troubles me that an MO would say such a thing.

Here's the real info:

prostatecancer.news/2022/06...

[kainasar]

This one shows the combo with Abi & OS pubmed.ncbi.nlm.nih.gov/377...