Abiraterone in "High-" and "Low-risk" Metastatic Hormone-sensitive PCa.

[pjoshea13]

New study below.

"Abiraterone acetate {Zytiga, Abi} received licencing for use in only "high-risk" metastatic hormone-naïve prostate cancer (mHNPC) following the LATITUDE trial findings."

"However, a "risk"-related effect was not seen in the STAMPEDE trial." "A total of 901 M1 STAMPEDE patients were evaluated after exclusions. Of the patients, 428 (48%) were identified as having a low risk and 473 (52%) a high risk."

"Patients receiving ADT + AAP had significantly improved OS {overall survival} (low-risk hazard ratio [HR]: 0.66 ... compared with ADT alone."

"Heterogeneity of effect was not seen between low- and high-risk groups for OS ..."

"For OS benefit in low risk, the number needed to treat was four times greater than that for high risk."

"Men with mHNPC gain treatment benefit from ADT + AAP irrespective of risk stratification for "risk" or "volume"."

***

Once again the term "ADT" is used to mean (post-DES) classic ADT. Abi is clearly a form of ADT, & could be used as such without the need for classic ADT. No doubt someone will come up with a better retronym than "classic ADT". "Castration therapy" would perhaps be clearer.

The term CRPC (castrate-resistant PCa) is clear enough, but what is the term for failing Abi monotherapy or Abi+classic ADT?

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/314...

Eur Urol. 2019 Aug 22. pii: S0302-2838(19)30620-7. doi: 10.1016/j.eururo.2019.08.006. [Epub ahead of print]

Abiraterone in "High-" and "Low-risk" Metastatic Hormone-sensitive Prostate Cancer.

Hoyle AP1, Ali A2, James ND3, Cook A4, Parker CC5, de Bono JS5, Attard G6, Chowdhury S7, Cross WR8, Dearnaley DP9, Brawley CD4, Gilson C4, Ingleby F5, Gillessen S10, Aebersold DM11, Jones RJ12, Matheson D13, Millman R14, Mason MD15, Ritchie AWS5, Russell M12, Douis H3, Parmar MKB4, Sydes MR4, Clarke NW16; STAMPEDE Investigators.

Author information

1

The Christie and Royal Salford Hospitals, Manchester, UK; Genito Urinary Cancer Research Group and the FASTMAN Centre of Excellence, Division of Cancer Sciences, The University of Manchester, Manchester, UK.

2

The Christie and Royal Salford Hospitals, Manchester, UK.

3

Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, UK.

4

MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK.

5

Royal Marsden Hospital, Sutton, UK.

6

UCL Cancer Institute, University College London, London, UK.

7

Guy's & St Thomas NHS Foundation Trust, London, UK.

8

St James University Hospital, Leeds, UK.

9

Institute of Cancer Research, Sutton, UK.

10

Division of Oncology and Haematology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Christie Hospital, Manchester, UK; University of Manchester, Manchester, UK; Swiss Group for Cancer Clinical Research (SAKK), Bern, Switzerland.

11

Department of Radiation Oncology, Bern University Hospital, Switzerland.

12

Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK.

13

Northampton, UK.

14

Stockton-on-Tees, UK.

15

University of Cardiff, Cardiff, UK.

16

The Christie and Royal Salford Hospitals, Manchester, UK; Genito Urinary Cancer Research Group and the FASTMAN Centre of Excellence, Division of Cancer Sciences, The University of Manchester, Manchester, UK. Electronic address: [e-mail].

Abstract

BACKGROUND:

Abiraterone acetate received licencing for use in only "high-risk" metastatic hormone-naïve prostate cancer (mHNPC) following the LATITUDE trial findings. However, a "risk"-related effect was not seen in the STAMPEDE trial. There remains uncertainty as to whether men with LATITUDE "low-risk" M1 disease benefit from androgen deprivation therapy (ADT) combined with abiraterone acetate and prednisolone (AAP).

OBJECTIVE:

Evaluation of heterogeneity of effect between LATITUDE high- and low-risk M1 prostate cancer patients receiving ADT + AAP in the STAMPEDE trial.

DESIGN, SETTING, AND PARTICIPANTS:

A post hoc subgroup analysis of the 2017 STAMPEDE "abiraterone comparison". Staging scans for M1 patients contemporaneously randomised to ADT or ADT + AAP within the STAMPEDE trial were evaluated centrally and blind to treatment assignment. Stratification was by risk according to the criteria set out in the LATITUDE trial. Exploratory subgroup stratification incorporated the CHAARTED criteria.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The primary outcome measure was overall survival (OS) and the secondary outcome measure was failure-free survival (FFS). Further exploratory analysis evaluated clinical skeletal-related events, progression-free survival (PFS), and prostate cancer-specific death. Standard Cox-regression and Kaplan-Meier survival estimates were employed for analysis.

RESULTS AND LIMITATIONS:

A total of 901 M1 STAMPEDE patients were evaluated after exclusions. Of the patients, 428 (48%) were identified as having a low risk and 473 (52%) a high risk. Patients receiving ADT + AAP had significantly improved OS (low-risk hazard ratio [HR]: 0.66, 95% confidence interval or CI [0.44-0.98]) and FFS (low-risk HR: 0.24, 95% CI [0.17-0.33]) compared with ADT alone. Heterogeneity of effect was not seen between low- and high-risk groups for OS or FFS. For OS benefit in low risk, the number needed to treat was four times greater than that for high risk. However, this was not observed for the other measured endpoints.

CONCLUSIONS:

Men with mHNPC gain treatment benefit from ADT + AAP irrespective of risk stratification for "risk" or "volume".

PATIENT SUMMARY:

Coadministration of abiraterone acetate and prednisolone with androgen deprivation therapy (ADT) is associated with prolonged overall survival and disease control, compared with ADT alone, in all men with metastatic disease starting hormone therapy for the first time.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS:

Abiraterone; Adjuvant treatment; Advanced; Androgen deprivation therapy; Hormone-naïve prostate cancer; Hormone-sensitive prostate cancer; Metastatic; Prostate cancer; STAMPEDE trial; Systemic therapy

PMID: 31447077 DOI: 10.1016/j.eururo.2019.08.006

[LearnAll]

I would not lose myself in the jungle of clinical trials as there are many contaminating factors in them

Looking directly, Abiraterone BLOCKS an enzyme called CYP17A1....and this enzyme is necessary for production of testosterone in human body.

Testosterone is produced from THREE different sites..(1) testicles (2) Adrenal Glands and

(3) prostate cancer cells themselves.

Abiraterone is the only UNIQUE medicine that blocks testosterone at all these three sites

So , this blockage of all sites kicks down testosterone to almost zero ,thus starving prostate cancer cells.

Now, this happens whether its high risk OR low risk metastatic cancer...!!!!

[DarkEnergy in reply to LearnAll]

I hear you, currently participating in a clinical trial of one!

If my Lupron Brain still has some fuel, (think) remember your response to my post (few months ago?) about, genotype, phenotype and environmental factors, including nutrition, plays a part in getting prostate cancer was not probable.

The reason I'm bringing this up, is the inclusion and exclusion criterias of clinical trials, is pseudoscience. And biology is mathematically adversed, well at least at the moment.

If this was not you, then I apologize, my point, we can build an airplane with mathematics, and it will fly on the first try...

[GP24]

Patrick,

could you comment this study? I guess this will be practice changing. But as Dr. Ryan pointed out, what do you do if you become resistant while taking this combination?

urotoday.com/center-of-exce... (at 2: )

GP

[pjoshea13 in reply to GP24]

GP,

I'm wary of commenting because 15 years ago I decided that Lupron was to be avoided as long as possible. At age 56, I didn't see the point of rushing into palliative treatment that failed for most in 2 years & induced the emergence of a less manageable cell type.

With ADT add-ons we get a longer mean-time to failure but an even less manageable cell.

I understand the urge to treat & some need aggressive treatment from the start, but I figured that, with no co-morbidities, I was good for another 25 years if I didn't have PCa & perhaps only 5 years if I rushed into ADT.

At 76, say, the math is quite different.

The last doctor I spoke to said that I was lucky to have indolent cancer. I didn't argue. I could have told him about the times that my PSA doubling time was at 3 months. There are many things I do which help to manage the disease. Nalakrats has hit on most of them (& others) & his cancer type is very difficult to manage. There are things that can be done that do not provoke the cancer.

Why I am wary of answering is that I would never advise anyone to do what I did.

-Patrick

[LearnAll in reply to pjoshea13]

In this atmosphere of fear mongering from many quarters...how do you know how aggressive you need to be in treating the cancer ?

I have a gut feeling that my cancer is mild and I might last many years but standard of care stuff from my doctors and my own hidden fears prompt me to go with the flow of proposed treatment. I had initial PSA of 830. Today exactly 100 days (on casodex,then Lupron and zytiga) it has dropped down to 2.3. No symptom ...feel fine. ADT of course has made me a semi tired, less active man...

[Hidden in reply to pjoshea13]

ok, but you have been on estrogen (BAT) that is a sort of ADT, no?

[pjoshea13 in reply to Hidden]

BAT was started late last year. Prior to that I used 3-months T followed by Prostasol for 3 months (agreed, a form of ADT) for years. & prior to that, for over 5 years, continuous T controlled the PSADT.

I have never been on Lupron, etc. However, I have been using DES for the past 3 months.

For quality of life, the 3 months of T after 3 months of ADT was wonderful. With BAT, the T period is too short.

-Patrick

[Hidden in reply to pjoshea13]

Didn't know about continuous T! Was it high dose? Did it bring PSA down?

[pjoshea13 in reply to Hidden]

After my failed surgery & failed salvage radiation, I felt that I had nothing to lose by trying T. I was aiming for high-normal & maintained a 1,000+ ng/dL. I tested monthly & the PSA did not change for 6 months. I was amazed. & then I began injecting vitamin B12 & the PSA began rising again.

But things calmed down a few months after I stopped the B12 & my PSA doubling time increased to over 24 months at one point. Inevitably, it began shortening, but slowly. So I had some pleasant years on continuous T.

I never produced much PSA (was 0.8 when a nodule was detected), so when it rose above 50, I started knocking it down. It took 3 months to knock it down to low single digits & 3 months of T to build it back up. Not sure why I switched to BAT - but approaching 15 years I figured I needed to be more aggressive.

Best, -Patrick

[Hidden in reply to pjoshea13]

quite amazing, so after high T 6 months PSA not moving it got till 50, then you have been on 3 months Prostasol and 3 months T with PSA between one digit and 50 and this for years! what about scans during this long time? did they show anything, did you have mets radiated? what was your Gleason (sorry, I forgot)?

[pjoshea13 in reply to Hidden]

I have known quite a number of men who regularly flew across country to get the most up-to-date imaging, but I never did. The question was "What would I do if something was found?"

Eventually, I had a scan because of leg pain & a lesion was found at L5 - unrelated to the pain. It might have been there some years. At that time, the practice was to radiate only if there was pain, but I found a radio-oncologist who was willing to radiate oligo-mets (this was 4+ years ago).

But when I switched to BAT in Oct, 2018, I made the mistake of thinking that the one-month cycle was good for everyone. In late January, I developed sciatica which lasted 6 months. A bone scan in April showed nothing that would explain the pain. I was sent to a neuro-bone guy who thought it must be caused by cancer. He ordered an MRI, which was not approved by insurance. My radio-oncologist therefore ordered a 2nd bone scan, which I thought was a waste of time. But it showed a tiny spot at S1 (sacrum).

Meanwhile, I had decided to try a 2-month BAT cycle. I had barely started the 2nd month when the pain started to go away. It seems that testosterone cypionate injected into my thigh lingers too long - not enough castrate days in a 1-month cycle.

The radiologist offerred to zap S1, but I declined. No point in using-up that option if a 2-month BAT is effective. My PSA at the end of the last 1-month cycle was 23.8. My PSA this week, at the end of the first 2-month cycle is 5.6. The cycles are too short to bring the PSA down its nadir in one cycle, but I expect to see declines in the following cycles. It appears that I do not have CRPC yet.

-Patrick

[tango65]

Thanks Patrick.

[Jbooml]

This kind of news makes me wonder if zytiga can be as trusted as standard ADT and again bolstered with yet additional treatment cocktail constituents...we seem to all have our own side sauce that through trials might prove even stronger than these two global PC combatants combined. It wouldn't take much to design an assortment of such triple combined therapies with those of us already so self administered. I take turmeric/pepper along with the formentioned and would love to see what head to head matchups with other's choices might illuminate.