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Abiraterone+docetaxel+ADT for newly diagnosed metastatic men beats docetaxel+ADT (or abiraterone+ADT)

Tall_Allen profile image
Tall_Allen

The first results of long-awaited PEACE-1 trial are in. They randomized newly diagnosed metastatic men to either prostate radiation or abiraterone or standard-of-care (SOC). SOC included docetaxel for many of the men.

Radiographic progression-free survival increased by 2.5 years (from 2.0 to 4.5 yrs) with addition of abiraterone to docetaxel. Time to castration resistance increased by 1.7 yrs (from 1.5 to 3.2 yrs).

The full results will tell us how much the prostate radiation adds, and the effect on overall survival. The analysis by metastatic burden will be important too.

Meanwhile, docetaxel+abiraterone+ADT should be considered the new standard of care.

meetinglibrary.asco.org/rec...

73 Replies

It would seem that over and over again, that multi-vector cocktail approaches work best with adaptive diseases like cancer (or Covid for that matter).

There is some not so old statistical research I recollect that backs of this up.

When you have an adaptive adversary, you hit it hard and early with everything you have... reducing the number of opportunities it statistically has to adapt.

that's what I tried to convince my doctors to do, but noooo... I got on ADT+Abiraterone (cf. LATTITUDE) the day on diagnosis, but not chemo... I also got radiation to the prostate, but I wanted to have had chemo too to increase my prognosis.. Now I am fighting to get PARP-inhibitor (I have BRCA2 - hence my aggressive cancer and this terrible diagnosis at 45 years old), but nooo... no PARPs are approved in DK.. not even for CRPC. and I don't full fill the inclusion criteria for any trials.. And I am still considered sensitive.. BUT.. my PSA just started to rise after 1.5 years from diagnosis. PSA decreased from initial 88 to <0.10 over 9 months and stayed undetectable for 6 months... but now the last month it rose to 0.15.. a check 3 days later said 0.16.. Now waiting for another PSA in 2 weeks (3 weeks after the last one)... If it is still on the rise.. Well, then I am possibly become castrate resistant :-( Now docetaxel has a poor effect.. Should have had it from the start together with the ADT+Zytiga+Radiation as I wanted.. Darn... this is tough when you are denied to have the treatment you want.. no free choices here, even though you are doomed and no possible ways to survive this.. Should be possible at this young age with this prognosis to go gamble rather than have treatment with evidence of death...

Strange thing about these trials is that individual experiences vary widely. There are men that stay progression free for years on Lupron alone. Meanwhile I got ADT+docetaxel+Abiraterone after my initial diagnosis and progressed to neuroendocrine cancer in roughly 15 months, or less than a year if you go by the earliest onset of symptoms instead of test results. That's one of the risk of aggressive treatments, in a small percentage of men it can cause treatment emergent neuroendocrine disease.

FWIW, my PSA was also starting to creep up and 3 cycles of cabazitaxel knocked it back to 0.03 and stopped progression in a rib. Pity it didn't have any effect on the neuroendocrine cancer.

Tall_Allen profile image
Tall_Allen in reply to tom67inMA

I doubt your case was treatment-emergent, it was probably there from the start, as a mixed type of NEPC with acinar adenocarcinoma PC.

tom67inMA profile image
tom67inMA in reply to Tall_Allen

I've actually gotten three different opinions from three different oncologists. My primary oncologist agrees with you. Dr. Beltran said it was treatment emergent. My radiation oncologist said it's likely neuroendocrince cancer of the bladder, not the prostate.

BTW, my original biopsy indicated likely intraductal carcinoma instead of acinar adenocarcinoma. This was backed up by the biopsy of the tumors surgically removed from my bladder. One was low grade bladder cancer, the other looked like intraductal carcinoma from the prostate. No two cases of prostate cancer are exactly alike, but I usually feel like a zebra amongst a herd of different colored horses.

Thank you Some good news

Am I reading too much into this? To me, RFS increase of 2.5 years is a huge number.

What about SEs? Are they worse?

Schwah profile image
Schwah in reply to TomTom1111

They specifically say in the study no major additional SEs. And yes...huge. In a world often measured in a couple of months for addionsk survival time fir new treatments, it’s almost unheard of for new treatment protocol to more than double the SOC numbers. Amazing.

I agree with Schwah- HUGE! The serious SEs were not much worse than docetaxel alone. I'll write a more detailed article about it, but these are only early results. The researchers knew this was big news so they wanted to get it out ASAP.

Thanks so much for sharing this..and for all you do. By citing the study names, you help the men’s discussions with their physicians. Your explanation of the studies is wonderful, too.

Burnett1948-Tall_Allen is it possible to start and benefit from the peace-1 cocktail now after being diagnosed metastasized last August 2020 when I started hormone alone?

I translated the latin "de novo" as "newly diagnosed" for ease of explanation, but what it really means is that when they were diagnosed, they already had metastases. So you are definitely in that category. It is distinguished from men who have already been treated with the hope of a cure, with RP or RT, but have failed and were later found to have metastases (recurrent or persistent). I'll explain this distinction more when I write up an article.

Great to see these new results. Thanks for posting.

That's significant data so far in this trial. My treatment was SOC (aberaterone+ADT + RT but no Docetaxal. Will this new approach takes it place?

They haven't yet published the data on the RT leg of the trial, but I expect it will be similar to STAMPEDE - only useful if the metastatic burden is low. But they also showed that abiraterone+docetaxel improved results regardless of RT.

Thanks for posting, TA. Does this also apply in my situation please?

Tall_Allen profile image
Tall_Allen in reply to Ahk1

All of these men were "de novo" - newly diagnosed with metastases. You are recurrent, which is different. But it is worth discussing with your oncologist.

Thank you for posting this TA. I will discuss it with my oncologist when I see her next month. It sounds like I should add abiraterone now before my PSA starts increasing.

The full study needs to be read and understood in details before buying in a knee jerk reaction. Its very tempting to believe it. ]

The funding for this study comes from PHRC/pharmaceutical company...

Can some one tell me full form of PHRC ?

.I am reserving an opinion until going into a detailed reading and understanding of this study.

I will be interested to find out what sample of patients the study chose.. were they simple, non aggressive type or aggressive variants ? Logically, aggressive variants need more and stronger assault . But simple low grade Adenocarcinoma does not need intensive assault with multiple treatments simultaneously.

The biggest pitfall of drug company financed studies is that they lump all patients into one category and their assumption is that every patient have "aggressive" PCa. This is far from truth. There are different shades of grey.

There are varying shades of aggressiveness in different men's cancers and I still believe

the treatment should be tailored according to the degree of aggressiveness of one's PCa.

Determining degree of aggressiveness is a tedious process as it requires dozens of biomarker, histological and imaging testing and understanding the composite picture of a man's PCA. This is money and time consuming and certainly does not fulfill drug companies goal of maximizing sales of expensive treatments. Take the results with a pinch of salt until we get an objective, detailed analysis of fine prints of this study. BTW, I do recognize many names in list of researchers and know that they are paid directly or indirectly by big pharma.

Tall_Allen profile image
Tall_Allen in reply to LearnAll

As usual, you are letting paranoia get in your own way. The trial was fully funded by UNICANCER. UNICANCER is the French equivalent of the US NCCN - a network of top French cancer hospitals.

unicancer.fr/en/unicancer

The drugs for the trial were contributed by drug companies who had nothing to gain because abiraterone and docetaxel are no longer covered by patents.

These are the top researchers in France. I recognise the names because of the ground breaking work they are justly famous for.

There is no conspiracy.

A maybe stupid question…? I did start ADT in Nov. 2019. In February 2020 I did start Abirateron + Prednison. My PSA is <0.05 since April 2020. Would it make sence to add now the Docetaxel (6 Sessions) while keeping ADT + Abirateron?

Tall_Allen profile image
Tall_Allen in reply to bwochf

Yes. Show your oncologist the abstract.

Exactly the question I was wondering about

Freaking amazing results. As I posted about my situation over 3 years ago, when I was newly diagnosed as metastatic, my MO (Dr Mark Scholz) advocated strongly for my using the triple cocktail of ADT/docetaxel/abiraterone, This despite no clinical proof that all 3 together worked better. His theory was that if early A+B was better than early B alone and early B+C was better than early B alone, shouldn’t A+B+C be even better. When I brought this protocol suggestion to the MOs at ucla for second opinion, they scoffed at the idea of using all 3 without a clinical trial. To learn now that “Radiographic progression-free survival increased by 2.5 years (from 2.0 to 4.5 yrs) with addition of abiraterone to docetaxel. Time to castration resistance increased by 1.7 yrs (from 1.5 to 3.2 yrs).” More than double the SOC. By the way, Scholz was using Zytega early with ADT many years before that became the new SOC.

There are some very important takeaways here besides the obvious. First, Despite all we still hear on this site about holding off certain treatments to delay CRPC, prevent earlier onset of more deadly forms of PC and ultimately delay death and suffering, the proven treatments of earlier use of the heavy guns is the best way to “delay CRPC, prevent earlier onset of more deadly forms of PC and ultimately delay death and suffering.” That fact is being proven over and over again in study after study. I urge those that are playing the deadly game of sequential use of these agents and even no use, to rethink their protocols. Secondly, search out an MO that is willing to responsibly think “out of the box”.

Finally, congratulations to TA who has been advocating early use of these combinations for years while continuing to fight the fight on all of our behalf’s.

Schwah

Tall_Allen profile image
Tall_Allen in reply to Schwah

Thanks. I fully agree. Maximally reducing the cancer load as early as possible increases survival.

In my case no scans confirmed Metastatic disease but high PSA had all docs convinced it was there. Any opinions on my case in relation to this trial specifically?

They detected metastases using bone scans/CTs or MRIs for lymph nodes. In STAMPEDE, docetaxel was not beneficial among men with no detected metastases.

6357axbz profile image
6357axbz in reply to Tall_Allen

Would docetaxel be effective after all mets have been zapped?

Tall_Allen profile image
Tall_Allen in reply to 6357axbz

Zapping metastases only destroys the ones big enough to show up on a PET scan (at least 5 mm). For every one you can see, there are thousands too small to be seen. No one knows if there is any benefit to zapping metastases, but there is a proven benefit to systemic therapy.

6357axbz profile image
6357axbz in reply to Tall_Allen

I’ve messaged Dr. Corn at MDA, reporting what you summarized about the Peace-1 trial and providing the link and asked him if he thought there are benefits to adding docetaxel to my plan.

Dett profile image
Dett in reply to 6357axbz

If you don’t mind, could you report on his feedback?

6357axbz profile image
6357axbz in reply to Dett

Sure

6357axbz profile image
6357axbz in reply to Dett

This is what Dr. Corn had to say regarding the Peace-1 trial results and if he thinks adding docetaxel would benefit me:

“Very interesting data and will be helpful to study further once it is published.

Your question is a good one but not sure- one of the challenges (in my view) is that the trials do not always answer the issue of sequencing.

For example, if you do not get abiraterone with docetaxel "in the beginning" but do "get later", will you do as well as if you get "all in the beginning"?

Not all the patient on the trial that got docetaxel up front got abiraterone later...

Anyhow, need to consider further.

Like you, I also wonder about disease burden - fortunately, yours is on the "low" side....I would imagine higher burden patients might benefit most from these combinations.”

Tall_Allen profile image
Tall_Allen in reply to 6357axbz

Read the section about burden of metastases. It is highly controversial. I think Europe, the UK, Canada, and the AUA got it right, and ASCO and NCCN got it wrong because they relied on an underpowered subgroup analysis. I also quibble with the CHAARTED definition of "low burden": if one has 10 metastases but they are all along the spine and the pelvis, they count it as "low burden."

6357axbz profile image
6357axbz in reply to Tall_Allen

I don’t find the section about burden of metastases. Could you kindly steer me there?

Tall_Allen profile image
Tall_Allen in reply to 6357axbz

The subtitle says: "Does docetaxel only benefit mHSPC patients with a high-volume of metastases?" About halfway down.

6357axbz profile image
6357axbz in reply to Tall_Allen

I must be a moron. Your summary above includes a link to an abstract. That abstract contains a link to the clinical trial description. I’ve scanned those both pretty closely but don’t find it. Is there another document I should be looking at?

Tall_Allen profile image
Tall_Allen in reply to 6357axbz

Sorry - my bad. I linked my own analysis yesterday in a different thread:

prostatecancer.news/2021/05...

6357axbz profile image
6357axbz in reply to Tall_Allen

Thanks

6357axbz profile image
6357axbz in reply to Tall_Allen

Paul Corn raises a good question:

“For example, if you do not get abiraterone with docetaxel "in the beginning" but do "get later", will you do as well as if you get "all in the beginning"?”

Also, I seem to remember data showing LU177 less effective on those with previous chemo...

All valid considerations I think.

Tall_Allen profile image
Tall_Allen in reply to 6357axbz

He may be right that there is some, as yet, undiscovered interaction between abiraterone and docetaxel. But that is doubtful. 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. So why not start them both earlier, since PEACE1 showed the toxicity of the combination was not much worse and the benefit was considerably more?

You are mistaking association with causation. Lu177-PSMA-617 is less effective when the cancer is more progressed. Mostly chemo is used when the cancer is more progressed (and it's less effective and more toxic then too). It's just a time-association. There is no known biologic interaction.

6357axbz profile image
6357axbz in reply to Tall_Allen

Would low wbc and rbc count preclude getting docetaxel? Mine are still low, presumably due to the radiation I received to zap my bone mets, especially the ilium which contains a lot of marrow.

Tall_Allen profile image
Tall_Allen in reply to 6357axbz

Sometimes docetaxel is given with Neulasta and Claritin. Discuss with your oncologist.

6357axbz profile image
6357axbz in reply to Tall_Allen

Thanks TA

Dett profile image
Dett in reply to Tall_Allen

Could you please clarify something, TA? Your write up is titled “Abiraterone+docetaxel+ADT for newly diagnosed metastatic men beats docetaxel+ADT (or abiraterone+ADT)”. But your summary chart does not show results for the PEACE1 trial for men for whom treatment was just ADT+abiraterone (i.e., no docetaxel). Were the ADT+abi men investigated as a distinct group as part of PEACE1? If not, is it fair to claim that subsequently adding docetaxel (while still hormone sensitive) would result in a similar large increase in time to progression?

Tall_Allen profile image
Tall_Allen in reply to Dett

As explained in the article, abi and docetaxel have equivalent results.

Dett profile image
Dett in reply to Tall_Allen

Clearly, I’m missing something. Per the summary chart, the time to progression in the PEACE1 trial with ADT+docetaxel is 2.0 years. In LATITUDE (abi), it’s 2.8 years (with a much higher/high risk population). In STAMPEDE (abi) the time to progression was not even reached after 3.4 years. STAMPEDE (docetaxel) time to progression was 3.1 years. How are these the same?

Tall_Allen profile image
Tall_Allen in reply to Dett

For abiraterone: In LATITUDE, progression was delayed by an extra 1.6 yrs by abiraterone; in STAMPEDE, they gained at least 1.4 years.

For docetaxel: In STAMPEDE, they gained 1.4 years; in CHAARTED they gained 1.1 years.

So understanding the differences in patient characteristics, they are all roughly similar.

More importantly, there was a randomized clinical trial where newly diagnosed men entering the STAMPEDE trial were randomized to either docetaxel or abiraterone. This is explained in the fourth paragraph, with 3 bullet points that you can read for yourself.

Dett profile image
Dett in reply to Tall_Allen

Re your first three paragraphs, those gains were with respect to ADT alone. I was comparing the ADT+abi and ADT+docetaxel results to the PEACE1 results for abi+docetaxel+ABT. I read your synopsis of the ‘randomized clinical trial’ results re abi versus docetaxel. Is this trial part of STAMPEDE or something different? This all gets very confusing.

In any case, the PEACE1 trial shows that adding abi to ADT and docetaxel results in a substantial delay in time to progression. It appears that you’re extrapolating that since abi and docetaxel seem to have similar outcomes in some studies, that adding docetaxel to ADT+abi will have the same outcome as adding abi to docetaxel and ADT. I have no idea, but is that accepted practice in clinical studies?

I don’t mean to be difficult, but my husband is a whole lot smarter than me and he will ask these kind of questions if I can get him to read this study and the DU comments. So far, I’ve been unsuccessful. It is going to take a lot of convincing to get my husband to go through chemotherapy, which he dreads.

Tall_Allen profile image
Tall_Allen in reply to Dett

I was showing you that abi and docetaxel have similar results independently, which seemed to be your question,

I promise that I did not make up the results of the combination. That's exactly what the PEACE1 RCT did.

Your husband may be outsmarting himself by avoiding the best evidence available. Avoidance is never a good choice.

Ahk1 profile image
Ahk1 in reply to Tall_Allen

TA, but I am only metastatic by psma. With conventional imaging I am not metastatic. Very hard decision for me now.

Tall_Allen profile image
Tall_Allen in reply to Ahk1

All of the clinical trials are based on detection by bone scans/CT. All the decisive RCTs will eventually be redone, but that will take decades. IMO - a met is a met. An M1 met indicates systemic spread and must be treated systemically. For every met you can see on any kind of imaging, there are thousands more you can't see on any imaging. I don't really get why it's a hard decision.

Ahk1 profile image
Ahk1 in reply to Tall_Allen

Thanks, TA. when I started ADT alone, my psa initially went down from 1.8 to .05 then it went up to .07. At that time , I asked my MO to add another drug and he said NO, let’s wait and see and get benifit eifits from Firmogon, so I said OK and knowing that he has a great reputations, I didt say anything and think he knows his business for sure. Now, my psa went down to .06 which you said to me a while ago, it’s just random changes. This is the reason why it’s hard decision, not sure if I should ask him again or wait.

Schwah profile image
Schwah in reply to Ahk1

Tall Allen is right. Why is it a hard decision? There are now double blind clinical studies that prove using more of these drugs earlier extends hormone sensitivity , extends time to disease progression and extends life. It is no longer a question. It is as close as we can get to a scientific certainty. Others may argue that a small subsection of men are better off waiting. They may be right, but we can not know if they are and even if it were true we have know way of knowing who that small subset of men are.

Schwah

Interesting...thank you!!

This describes my husband. One month ago today he started docetaxel and ADT. I know it’s outside of the study protocol to start him on abiraterone now, but it sure sounds like a great idea. He was de novo just a few weeks ago!

Tall_Allen profile image
Tall_Allen in reply to bethdavis

It sounds perfect for him.

bethdavis profile image
bethdavis in reply to Tall_Allen

I already messaged his doctor! Thank you!

it is advised that those of us on Firmagon, for example, might do better switching to docetaxel or is staying on Firmagon best?

bethdavis profile image
bethdavis in reply to spencoid2

Firmagon is a form of ADT. Docetaxel is chemotherapy. My husband is on both.

This study indicates that he would further benefit by the addition of abiraterone. I messaged his team at Mayo about it.

spencoid2 profile image
spencoid2 in reply to bethdavis

yes, and hoping to get off ADT, not tolerating it too well.

bethdavis profile image
bethdavis in reply to spencoid2

ADT is the mainstay of therapy. There are lots of tips here that might help you. Exercise is very helpful.

Tall_Allen profile image
Tall_Allen in reply to spencoid2

You will never get off ADT of some kind if you are metastatic.

spencoid2 profile image
spencoid2 in reply to Tall_Allen

oh great my favorite. i thought chemo and radiation together could eliminate ADT. i guess i need to get used to it. the new old me.

Thank you TA for posting this, really helpful, as ever. I'm hormone sensitive still, 0.07PSA but on Enzalutamide and ADT since July 2020, not Abiraterone. This is the SOC in England and Wales. Would you recommend me asking my Oncologist to start the Docetaxel now, rather than wait for the Enzalutamide to fail? Thank you. Graham

Tall_Allen profile image
Tall_Allen in reply to lcfcpolo

Absolutely!

Tall Allen In simple terms,,, the 1trial is while xtandi or all other adt treatments are still working wellbringing your psa down it is best to bring in docetaxel in the treatment run? My pa got diagnosed 1 yr ago In June and was put straight on xtandi and adt every 3 months, due to the pandemic they wouldn’t do chemotherapy do you think it is worth asking is mo about this while his treatment is being Successful? I’m not great at understanding it in so much detail and really need it in simple terms, I am England so appreciate that treatment may be different here, thank you so much in advance.hope your well x

Tall_Allen profile image
Tall_Allen in reply to Jack02

Yes, definitely ask. The combination improves survival - probably similar with enzalutamide as abiraterone.

This is so great!

Is there anything sacred about 6 infusions of docetaxel? Can or should this be varied for different individuals?

Tall_Allen profile image
Tall_Allen in reply to 6357axbz

Sometimes they go as high as 10 if it is well-tolerated.

Thanks T.A. for the news flash, this has been on my mind for a while. I’m metastatic and just under 2 years out from starting taxotere and ADT. PSA went timely from 13 to 0.006 and has stayed undetectable. I’m not newly diagnosed and have seen different opinions on adding Zytiga to ADT at this time and would like your input.

Tall_Allen profile image
Tall_Allen in reply to pupcat

The technical term is "de novo." What it means is that the patient hasn't had some other treatment first. In PEACE1, docetaxel alone was effective at preventing progression for a median of 2 years (as it is currently doing for you), but progression was delayed much longer (for a median of 4.5 years) when Zytiga was added to the mix. I think you should email the abstract to your MO and talk to him about it.

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