BAT+ Olaparib in men with CRPC

[pca2004]

New paper below [1].

Michael Schweizer is not as well-known as Samuel Denmeade to those interested in BAT.  Here he is speaking to Alicia Morgans a year ago.

urotoday.com/video-lectures...

From a more recent discussion between Charles Ryan & Emmanuel Antonarakis [2]:

Charles Ryan: I mean, you're basically taking... if I can use the term, the evolutionary biology of prostate cancer and just reverting it, because what you are saying is all of the progression and death from prostate cancer is because we starve, starve, starve the testosterone, the androgens, and cancer evolves, whether it's neuroendocrine or p53 emerges, et cetera. And you're just saying, "Don't give them that opportunity or revert that." In a way, it's almost convincing the cells that they are happy with the testosterone on board and they won't progress to these lineage plasticity-type events.

Emmanuel Antonarakis: Yeah. That's-

Charles Ryan: That's a paradox.

Emmanuel Antonarakis: That's the hypothesis. I just want to mention two other things so we can put a plug in for our fellows who became faculty members. We had a fellow, Michael Schweizer, who is, of course now at the University of Washington in Seattle. Dr. Schweizer has done a study, it's been presented at ESMO but not yet published; a single-arm study, no control group, where patients got bipolar androgen therapy plus the PARP inhibitor, olaparib.In that study, the combination of BAT plus olaparib produced a PFS, a radiographic PFS that was more than 12 months, which was longer than we had previously seen with BAT monotherapy. Now, this was not a controlled study with a control group, but that 12 plus month PFS was very intriguing. I have not yet seen the breakdown by HRR status because, in that trial, he allowed both the HRR deficient and proficient, but you may have your own hypothesis.

More Schweizer: [3].

***

It's strange that the cohort that had no DNA defects did as well as the cohort that did.  Perhaps that indicates that supraphysiological T really does induce double-strand DNA breaks? 

I wish that someone would compare the effect of T at 2,000 ng/dL versus the normal-high of 1,000 ng/dL.

From the paper:

"Results: Thirty-six patients enrolled and 6 discontinued prior to response assessment. In the ITT cohort, PSA50 response rate at 12-weeks was 11/36 (31%...), and 16/36 (44%...) had a PSA50 response at any time on-study. After a median follow-up of 19 months, the median clinical/radiographic progression-free survival in the ITT cohort was 13.0 months (95% CI 7-17). Clinical outcomes were similar regardless of HRR gene mutational status.

"Conclusions: BAT plus olaparib is associated with high response rates and long PFS {progression-free survival} Clinical benefit was observed regardless of HRR gene mutational status."

-Patrick

[1]  pubmed.ncbi.nlm.nih.gov/365...

[2]  urotoday.com/video-lectures...

[3]  urologytimes.com/view/dr-sc...

[NPfisherman]

Patrick and smurtaw,

Thanks for the article and information. Indeed, there is more than one way to "skin the cat" called PCa. For me, I am holding onto BAT for later purposes, if necessary. This will be part of getting to a chronic disease state, and perhaps, part of the cure.. High testosterone feels a lot better than the androgen desert... and of course, Merry Christmas....

Fish 🐠

[Cooolone]

Using treatment to resensitize another treatment line use is an should be a primary result benefit that would put this main stream and maybe allow for a higher population study to focus on genomic markers or other indicators of WHO this would work for.

I believe someone here had posted about Steady State progression, the idea about knocking the PCa out completely maybe isn't the best way to deal with a slow (for most) disease. But knocking it down to barely moving, retarding it's progression to something you can manipulate and manage, might be a better paradigm. I was blown away a few years ago in my own experience with progression to learn that treatment itself actually teaches or pushes the PCa to change, and not always in a good way for the patient. How the drugs that help now, become our bane later...

And is (my opinion) why despite many different paths today in regard to treatment, the end points have not shifted much. It would be interesting to have a charted representation with overlays of each path along a timeline for a given diagnosis and the differentiating treatments and result endpoints. Yeah, they do it separately, but not together! I'm sure we would find not much deviation... But here, with a simple alternating path of drugs, a reset is possible? Amazing!

[MateoBeach]

Thank you so much for posting this Patrick. I had not seen it and it is obviously of very much interest to those like myself on some form of BAT. That Olaparib could improve and prolong BAT response in both those with and those without HRR mutations is eye opening. Considering that dsDNA breaks as one mechanism of action for Supra physiologic testosterone.

I appreciate the science and analysis you are bringing here in your posts. Reminds me of another Patrick. Best regards to you. Paul / MB

[NPfisherman]

BAT is very appealing to me for obvious reasons, but my MO is resistant when things are going well...Glad it has worked out for you..Enjoy the kids while young.They grow up too fast..

Fish

[cujoe]

I'm in Holiday mode for the next week or more - so not able/willing to dig below the surface of the recent posts/replies by our distinguished members here. However, my current boosted T (due to and on-going experiment with bical) to a level close to 800 has provided the same QOL boost that you speak of. I continue to say that all docs prescribing ADT should have to go on it for a min of 3 months before being allowed to recommend it to their patients.

At my most recent appointment I gave my MO a copy of the PDF article by Tim Baker, "Farewell Old Friend" and told him that he should circulate it throughout the MOs, RTs, and surgery groups at his cancer center. There is no way around the fact that Zero T = poor QOL.

Happy 2023 - and may it be one filled with lots of happiness, love, and exceptionally good health! Best to All! Ciao - Capt'n cujoe

PS In case you missed it, here is a link to Marnie's post with the Tim Baker's PDF download:

healthunlocked.com/fight-pr...