PEACE1 - the advantage of combining docetaxel and abiraterone in men newly diagnosed with metastatic PCA

[Tall_Allen]

Here's my article about it, as promised. I'll update it as more info comes in.

prostatecancer.news/2021/05...

[6357axbz]

Good article TA. Thanks

[Pwjpp55]

Good article, thanks. To ensure that I understand it correctly, should I assume that: 1) Abiraterone is given daily, 2) "regular" ADT treatments (Lupron, etc.) are given as prescribed (1 to 6 month injections, etc.), and, 3) doxetaxal is given in 6 to 10 sessions and then ended? Or did I miss something? Thanks!

[Tall_Allen in reply to Pwjpp55]

Yes, that is all correct.

[Cooolone]

I'm really bummed... This was definitely a topic of discussion with my MO prior to beginning Docetaxel therapy... ie, the addition of Zytiga to ADT & Chemo! A flat out rejection based upon the lack of data via RCT.

Now on my 5th cycle and heading to my 6th, wondering if there would benefit to begin adding it even now, the last 4 weeks or so of therapy?... Arrrgh! Let alone with such a profound (2x) benefit to do so if it was throughout the treatment duration... Or pushing to go to Zytiga now, and continue for 5-6 months as it would have been with the chemo...?

Thoughts...?

[Tall_Allen in reply to Cooolone]

This wasn't for cases like yours --It was only for de novo metastatic patients. But with your soft tissue metastases, I think a more aggressive treatment is worth discussing - the Zytiga added very little to toxicity.

[Cooolone in reply to Tall_Allen]

Well, wasn't I de Novo metastatic? mHSPC? What more aggressive therapy would apply aside from Immunotherapy? Curious...

[Tall_Allen in reply to Cooolone]

de novo mHSPC means not previously treated. You are recurrent/persistent mHSPC. it sounds like you had RP and SRT. I'm agreeing with you that adding Zytiga would be more aggressive.

[Cooolone in reply to Tall_Allen]

I got ya'... My misunderstanding as de novo I felt applied to the metastatic progression...

Thank you for clarification. And yes, I agree, I've already sent an email to my MO requesting discussion and possible addition of Zytiga Now for the remainder of my chemo and possibly keeping it for the cycle I would have with the chemo, ie, the 18 weeks total. The application may be a little offset, but whatever additional duration I may experience until progression would certainly be welcome. I'm well aware that it's not an if ... But a when! So any ability to delay it is beneficial! Funny thing is I know exactly what the first response will be, that it would be off label, not approved!... Lol

[Tall_Allen in reply to Cooolone]

You would continue the abiraterone until it stops working, not just until the end of chemo.

[MateoBeach in reply to Cooolone]

You could start the Abiraterone now and extend docetaxel to more cycles, up to ten, if you are tolerating it.

[cesces]

1. Thanks for the article.

2. "The authors found that patients born on a Monday benefited the most from abiraterone, and it was statistically significant."

How can that be statistically significant? Can't we rely on statistics?

3. Is there any reason to believe that these results will not apply to patients other than those recently diagnosed with metastatic cancer?

[Tall_Allen in reply to cesces]

1. You're welcome.

2. That was the point. There is much more to statistics than p values. It also has to be sufficiently powered to detect a meaningful difference, and that is difficult with subsets. Statistics can only be relied upon if the sample size is sufficient to account for both Type 1 and Type 2 errors.

3. Not from the Peace1 trial.

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

Monday's child is fair of face

Tuesday's child is full of grace

Wednesday's child is full of woe

Thursday's child has far to go

Friday's child is loving and giving

Saturday's child works hard for his living

And the child that is born on the Sabbath day

Is bonny and blithe, and good and gay.

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 05/24/2021 8:17 PM DST

[Brightman]

Thanks for a very informative article. So is it an advantage for me now to add Abiraterone to my regime?

I have been on ADT since I was diagnosed in 2016 with 4 mets, Gleason 9. I had 25 sessions of radiation and 6x 3 weekly Docetaxel infusions. After 4 years of nadir<0.01 my PSA increased to 0.16 and my PCa returned to my T10 vertebrae, which has since been radiated with SBRT.

[Tall_Allen in reply to Brightman]

I think it's a good idea to discuss it with your MO.

[nobaday]

Thanks for article. I first became aware of PEACE I in Jan 2018. I took the Canadian SOC route with Abiraterone + ADT as opposed to the more standard and cheaper docetaxel chemo + ADT in the US 3 years ago. I had lots of spine Mets at diagnosis.

I/we have been waiting for this PEACE I data for 3.5 years! I thought/ am not surprised the outcome would be Abiraterone+Docetaxel + ADT would better . ‘Hit Prostate Cancer with the kitchen sink hard and early’ . I have heard that message from many people through this site.

I am impatiently waiting for Lu177 to be approved as for me I view Lu177 as being a more selective treatment than docetaxel chemo for PSMA +ve patients. If Lu177 had been available in Jan 2018 in North America I would have gone for Lu177 + Abiraterone + ADT. Let’s hope the clinical trials keep doubling the survival time. I was given a bell curve average survival time of 2 years in Jan 2018. I’m now looking forward to 4 and 5 year anniversary’s.... maybe more??!!

[Northcaptain]

thanks for posting. What is the definition of a « de novo metastatic patients » What is the clinical and visible definition ?

[Tall_Allen in reply to Northcaptain]

It means "from the beginning," when you are diagnosed with metastases, before any treatment

[Concerned-wife]

Thank you for this. You help so many men and their loved ones with your analyses.

[Bdale]

Thanks TA, I have been on ADT+ABI since 11-2019, my PSA is 0.26. would adding Doxetaxel now make any sense?

[Tall_Allen in reply to Bdale]

You've been treated, so this really provides no direction for you, but it is definitely worth discussing with your MO.

[bethdavis]

I messaged my husband’s doc at Mayo immediately after seeing this the other day. Of course the PA answers, instead of Dr Kwon. She said that they were not familiar with these results, and we would discuss on his next appointment.

My husband gets his 3rd treatment of docetaxel on June 2, and we see Dr Kwon next on June 10. Do you think it is advisable to wait that long, or should we push for starting the abiraterone now?

Should he have additional chemo doses since we are midstream already?

He was de novo until April 21 when he had his first chemo and first ADT. Diagnosed April 2.

[Tall_Allen in reply to bethdavis]

That's only 3 weeks. The number of chemo infusions depends on how well he does with them.

[bethdavis in reply to Tall_Allen]

He is tolerating them well. I was just wondering if, following the study protocol, he would need to extend.

[Tall_Allen in reply to bethdavis]

The study protocol did not extend it.

[Tall_Allen in reply to Tall_Allen]

I was thinking about your question and perhaps you are making an assumption that chemo acts more effectively when Zytiga is present and vice versa. Perhaps. But they have very different ways of killing cancer cells. Docetaxel stabilizes microtubules so cancer cells can't divide. Abiraterone prevents the androgen receptor from being activated. They are two different targets. What PEACE1 shows is that hitting both targets as early as possible maximizes cell kill. Chemo is finished after just 15 weeks, but abiraterone continued to work for 4.5 years.

[Quick2019]

Thanks for the information !

[Flash64]

Thanks Allen, great article! I did Docetaxel + ADT when first diagnosed (2017) and added Abiraterone as soon as I finished Docetaxel, so hopefully my results will be somewhat similar to PEACE1.

[Tall_Allen in reply to Flash64]

I agree. Many doctors wanted to see signs of treatment failure on docetaxel before beginning on abiraterone. This shows just how much longer treatment failure can be delayed by not waiting for treatment failure on one before beginning the other.

[Cooolone in reply to Tall_Allen]

This is the premise by which I had my discussion with my MO. I understand completely the synergy that probably allows the Zytiga to extend it's effectiveness when applied together, but the "treatment before failure" concept has my attention and has me intrigued.

So I mentioned this but my MO, who is too entrenched, I believe fearful of not following the data from solid study results, going with what is know, than unknown. I'm not sure he will agree to beginning Zytiga now that my Docetaxel infusions is complete (6). I even discussed adding a few of those (infusions) as my tolerance has been fairly ok, and he wasn't enthusiastic about that either.

So we (patients) have to fight hard to counter the forces of the SOC, especially if we want progressive results, or the possibility of receiving them. Not sure what I'll do if I feel strong enough about beginning the Zytiga absent progression, but if he won't agree as I'm very happy with him... Again, a conundrum...

[Tall_Allen in reply to Cooolone]

I always email the link to the peer-reviewed article (or in this case, the presentation) ahead of the meeting to give him a chance to mull it over. The worst thing you can do is spring it on someone and demand an answer. I'm not saying you did that, just some advice from my experience. I seldom found (only once) a top MO who isn't willing to go beyond the SOC if approached correctly.

[Cooolone in reply to Tall_Allen]

No, most definitely, I agree. I sent the link to the abstract/summary and requested he review it, and that upon our next consultation, we discuss it. This was 2 weeks forward. I did express my favorable opinion toward it but also acknowledged the lack of data and specifics.

His reluctance is specific to going off script from the study path. I understand but don't necessarily agree. This was reasoning as well with the conversation in regard to MSI-H, but that I was a bit low, but still MSI bring present, he felt only when mCRPC was present that this would be worth exploring. Again, following the SOC and the numbers/data.

Once, early upon my Stg IV diagnosis, when "he" told me that the presentation of my PCa is extremely rare, this then tells me then that following the SOC may not be in my best interest.

Of course we won't really ever know, because you would need as many of "me's" as the treatments I would like to try, lol, and that's not reality of course. But my thinking is that there are characteristics associated with the PCa behavior. My spread to my Peritoneal and Appendix behaving more akin to Colon Cancer or Ovarian Cancer, lends me to think what worked well for those? Treatment like HIPEC comes to mind, etc. All these enter discussion... None with immediacy, but that they be looked as and considered seriously and not with a passing fancy. Specific to my condition and not in respect to the "Group" of patients eho are mHSPC...

In other words, due to my outside the box presentation of my cancer, that outside the box therapy be front and center, not used later as a last resort when the SOC fails!

[Tall_Allen in reply to Cooolone]

Working with a patient, I really only had the experience once of an MO who was unreasonably tied to the SOC. I tried to work with the MO, but eventually I suggested moving to a different MO at a different hospital. We are thrilled with our current MO who is very open to all reasonable suggestions.

Did you have tissue taken from the metastases on your peritoneum and appendix? If so, you might suggest that they send it to the Wang Lab at Duke and do the following IHC stains on it: AR (androgen receptor), PSA, PSMA, MSH2, MSH6, PD-L1, chromogranin A (CGA), neuron-specific enolase (NSE), synaptophysin (SYP), DLL-3, CD56, and Somatostatin (SST). I think quantitative proteomics will be more useful to you than any genomic analysis.

[Tall_Allen in reply to Tall_Allen]

I should add that the SOC that that one MO was tied to was based on one of several different guidelines (in that case, NCCN). He was a young MO, just starting out (lesson learned!), and didn't want to rock the boat. I pointed out how different professional organizations differed. He said that at his hospital they ONLY follow NCCN guidelines (and they aren't even an NCCN hospital). We went to another hospital. Most guidelines are written to be flexible.

[LastMohikan]

Dear TA, Thanks for the article. this January I had my first metastases 1 point in my bone, after StereotacticRT 3days, I started just Lucrin 3 monthly now I got second Lucrin injection. I asked to my MO whether we will add Zytiga or others he said not now. But article promise better things for me . I need your comments on it. Thanks...Umit

[Tall_Allen in reply to LastMohikan]

I already gave my comments - what is it you want to hear?