What happens after triplet therapy? - Fight Prostate Ca...

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What happens after triplet therapy?

Maxone73 profile image
22 Replies

To be honest, I hate to talk about this, I hope RIPTACs, immune therapies and new radiotherapies will be available soon (and the early clinical studies are really positive!), but let's recap the actual SOC as suggested by the latest big trials (I wish there were data for darolutamide as well).

At the EAU 2025 meeting, Dr. Bertrand Tombal discussed the limited efficacy of using a second androgen receptor pathway inhibitor (ARPI) in prostate cancer after progression on initial triplet therapy. The PLATO trial demonstrated minimal responses (1-2%) when combining ARPIs after progression. Guidelines generally advise alternative treatments like chemotherapy, PARP inhibitors, or LuPSMA therapy.

Thus, while typically not recommended, a temporary ARPI switch might be appropriate for certain patients, especially those initially treated with abiraterone, delaying more aggressive interventions.

prostatewarriors.com/2025/0...

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Maxone73
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Thinking about it is very scary to me. I try not to but it’s hard.

Maxone73 profile image
Maxone73 in reply toStayingOptimistic

I understand you, I am trying also to keep up with all the strategies and new therapies that are for people in hormone sensitive phase that aim at delaying castration resistance.

PCaWarrior profile image
PCaWarrior in reply toMaxone73

I hope that pBAT keeps me HSPC. I was supposed to go CRPC some time ago. Hasn't happened yet. Mateo is on a modified BAT. Still HSPC after 8-10 years... (I'm not sure exactly how long). Patrick is doing a modified BAT. Been about 20 years for him.

Not much data so every time I do an ADT PSA test, I hold my breath.

Maxone73 profile image
Maxone73 in reply toPCaWarrior

I won't be able to try BAT till there are some clinical trials results, no MO would dare to prescribe that here...I will have to wait till I get some news from oric-944 and similar!

PCaWarrior profile image
PCaWarrior in reply toMaxone73

23 trials. I'd post them but hu has text length limitations.

I'll post three

4. RESTORE

Trial and results: clinicaltrials.gov/ct2/show...

Summary: A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts

ncbi.nlm.nih.gov/pmc/articl...

Commentary: A Multicohort Open-label Phase II Trial of Bipolar Androgen Therapy in Men with Metastatic Castration-resistant Prostate Cancer (RESTORE): A Comparison of Post-abiraterone Versus Post-enzalutamide Cohorts - PMC

ncbi.nlm.nih.gov/pmc/articl...

Enrollment: 112 actual

Stage: CRPC

Summary:

1. Complete

2. Men who failed Xtandi or Zytiga received BAT therapy. After BAT therapy most of them were rechallenged with Zytiga or Xtandi.

3. Study was underpowered but the Initial PSA50 response appears to be better for post-Xtandi BAT vs. post-Zytiga BAT.

4. Excellent results (68% PSA50) for post-BAT Xtandi challenge.

1. TRANSFORMER

Trial and results: clinicaltrials.gov/ct2/show...

Commentary: TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer - PMC

ncbi.nlm.nih.gov/pmc/articl...

Enrollment: 222 actual

Stage: mCRPC

Summary:

1. Complete

2. BAT (1) vs enzalutamide

3. Excellent results (77% PSA50) for post-BAT Xtandi challenge.

2. Olaparib + BAT

Trial and results: clinicaltrials.gov/ct2/show...

Summary: ESMO 2021: Bipolar Androgen Therapy (BAT) Plus Olaparib in Men With Metastatic Castration-Resistant Prostate Cancer

urotoday.com/conference-hig...

Details: Clinical Study Protocol (CSP)

cdn.clinicaltrials.gov/larg...

Enrollment: 36 actual

Stage: mCRPC

Summary:

1. Complete

2. Several other studies testing olaparib in combination with DNA damaging therapies are underway or have recently completed. The results of these studies generally support combining PARP inhibitors with DNA damaging therapies.

3. Results of this study showed good response regardless of HRR status.

4. Testosterone enanthate or cypionate 400mg IM every 28 days. Olaparib 300 mg BID.

5. Excellent results for synergy with PARP inhibitor Olaparib. 47% of those who had an HRR mutation as well as 47% of those without an HRR mutation had a PSA50 response. 76% had a PSA drop. 26% had a PSA90 response. 61.5% had a radiographic complete or partial tumor response.

6. A control group was not included (Olaparib and injections of saline solution) but the radiographic response rate appears to be 1-2x what migjht be expected from Olaparib monotherapy.

PCaWarrior profile image
PCaWarrior in reply toMaxone73

A big one ongoing:

3. STEP-UP

clinicaltrials.gov/ct2/show...

Sequential High Dose Testosterone and Enzalutamide Compared with Enzalutamide Alone for the Treatment of Asymptomatic Metastatic Castration Resistant Prostate Cancer, STEP-UP Study

cancer.gov/about-cancer/tre...

Enrollment: 150

Stage: CRPC

Summary:

1. Estimated completion date 7/2025-7/2026

2. BAT (1) interleaved with Enzalutamide in two schemes

3. If successful, this could change the PCa paradigm. If enzalutamide sensitivity can be restored, darolutamide and apalutamide sensitivity should be restored.

Arm B shown.

Arm A receives constant Xtandi

Arm C repeats monthly T injections (56-day cycles) until progression, then 56-day cycles of Xtandi until progression.

PCaWarrior profile image
PCaWarrior in reply toMaxone73

One for HSPC

5. BATMAN

PSA provocation by bipolar androgen therapy may predict duration of response to first-line androgen deprivation: Updated results from the BATMAN study – PubMed

pubmed.ncbi.nlm.nih.gov/359...

PSA provocation by bipolar androgen therapy may predict duration of response to first‐line androgen deprivation: Updated results from the BATMAN study - Denmeade - 2022 - The Prostate - Wiley Online Library

onlinelibrary.wiley.com/doi...

clinicaltrials.gov/ct2/show...

Enrollment: 33 actual, 29 performed BAT.

Stage: HSPC

Summary:

Complete

1. BAT with a good HSPC scheme.

2. 6-month ADT lead-in. Alternating 3-month cycles of ADT and BAT (1)

3. 80% radiographic response rate.

PCaWarrior profile image
PCaWarrior in reply toMaxone73

I know a guy in Norway and his MO prescribed BAT. Modified even!

Maxone73 profile image
Maxone73 in reply toPCaWarrior

I am not in Norway 🤷‍♂️

PCaWarrior profile image
PCaWarrior in reply toMaxone73

Italy is as advanced as Norway.

Australia and Brazil also. (BAT MOs)

Maxone73 profile image
Maxone73 in reply toPCaWarrior

it's not a matter of being advanced, there are also great pharma companies in Italy, the problem is with the law, not approved medical treatments make a MD risk his license, my MO had to fight to get me into ARASENS because it was not yet approved in Italy, apparently if a research has not reached NEJM or the Lancet is not even considered, unless it's a clinical trial that is carried out here 🤷‍♂️ and at the moment there is no BAT trial

I have mentioned BAT to my MO from the beginning, his reaction was "I know about it, it's still like playing with a loaded gun till you can know who can benefit from it and you have an ATM mutation that could make things worse"

PCaWarrior profile image
PCaWarrior in reply toMaxone73

OK. I talked to some BAT researchers and decided to implement it. I wanted to stay HSPC and I wanted testosterone.

Some guys do it on their own. Most guys I know who are doing BAT let their MOs know. Some have MOs that prescribe it (the guy in Norway is one).

But I don't know how hard it would be in Italy. And if one is only willing to entertain SOC therapies, BAT is out for now.

addicted2cycling profile image
addicted2cycling in reply toPCaWarrior

"... Some guys do it on their own ..."

In 2015 at the consultation with Dr. Onik he asked why I chose castration instead of ADT. I explained and at that time he said he would get me on TRT after he completed his treatment. Beginning in January 2016 following his cryoablation of the GL10 in right half and IRE of GL6/GL7 in left half and his experimental Immunotherapy injection he got me on 200mg Cypionate bi-weekly. PSA remained low until 2018. Axumin Scan showed uptake and biopsy showed some GL6/GL7 that again was taken care of with IRE.

I stopped TRT and combined with IRE my PSA went back down so TRT was started again. Had rising PSA so stopped TRT and PSA responded by going down then began TRT again. 2023 had rapid PSA Doubling to 12 so stopped TRT and scheduled biopsy after PSMA PET/CT showed left side positive again. This time biopsy had 3 cores of 3+3 and since I had another PSA before biopsy with my PSA plummeting without TRT my plan was to simply Watch and Wait. Another BLOOD WORK on this coming Monday and if PSA is again .02 I plan on starting TRT again.

The PSA rollercoaster giving the *T* on/off/on /off .... has me feeling I'm still HS so will continue my own BAT experiment.

PCaWarrior profile image
PCaWarrior in reply toMaxone73

By the way, BAT studies arare in NEJM and the Lancet. And of course clinicaltrials.gov.

Maxone73 profile image
Maxone73 in reply toPCaWarrior

send me the links when you can, I will send them to my MO

Maxone73 profile image
Maxone73 in reply toPCaWarrior

stupid me, I can use perplexity to check if nowadays there is some BAT trial in Italy, you never know

PCaWarrior profile image
PCaWarrior in reply toMaxone73

Yeah, those AIs are already becoming ingrained. I have one that does nothing other than check movie ratings for me. Another to write poems and essays. Another one is my doctor. Another is a workout and supplement planner.

Professorgary profile image
Professorgary in reply toMaxone73

Is your MO waiting for trial results or FDA arrpoval? The trial results are out there but according to Denmeade FDA approval will probably not happen. My local MO won’t touch BAT because of liability concerns but fortunately Denmeade is only about 60 miles from me and my uro will work with Denmeade if I choose not to enroll in a trial.

JohnInTheMiddle profile image
JohnInTheMiddle in reply toPCaWarrior

Yup, because as we know, PSA stands for "Periodic State of Anxiety" 😳

Maxone73 profile image
Maxone73 in reply toStayingOptimistic

I have written this thinking about your situation:

healthunlocked.com/fight-pr...

Oldie68 profile image
Oldie68

There is also the APEX trial at Johns Hopkins. Another triplet therapy: BAT+eflornithine+xtandy. I failed the first one with less than a year staying CS. Hope this one will work better but I am not holding my breath. Just taking it day by day.

-db123_ profile image
-db123_

I wonder if anyone in trial has Intraductal and or Cribriform?

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