Advanced, non-metastatic PCa & Monotherapies.

[pjoshea13]

New Swedish study.

"In randomised controlled trials, men with advanced, non-metastatic prostate cancer (PCa) treated with anti-androgen monotherapy (AA) had similar all-cause mortality as men treated with gonadotropin-releasing hormone (GnRH) agonists. Using real-world evidence (i.e., observational data), we aimed to further assess the difference in mortality between these two drug categories."

"The cumulative 5-year PCa mortality was lower for men treated with AA (16% ...) than men treated with GnRH agonists (22% ...). The 5-year other cause mortality was also lower for men on AA (17% ...) compared to men on GnRH agonists (27% ...). In regression analyses, the risk of PCa death was similar, GnRH agonists versus AA (reference), hazard ratio (HR) 1.08 .., but the risk of death from all causes was higher for men on GnRH agonists, HR 1.23 ..."

"Our results indicate that the use of AA as primary hormonal therapy in men with high-risk non-metastatic PCa does not increase PCa-specific mortality compared to GnRH. Using AA instead of GnRH agonists may result in shorter time on/exposure to GnRH-treatment, which may reduce the risk of adverse events associated with this treatment."

-Patrick

ncbi.nlm.nih.gov/pubmed/303...

Acta Oncol. 2018 Oct 30:1-9. doi: 10.1080/0284186X.2018.1529427. [Epub ahead of print]

Anti-androgen monotherapy versus gonadotropin-releasing hormone agonists in men with advanced, non-metastatic prostate cancer: a register-based, observational study.

Thomsen FB1, Bosco C2, Garmo H2,3, Adolfsson J4, Hammar N5,6, Stattin P7, Van Hemelrijck M2,5.

Author information

1

a Copenhagen Prostate Cancer Center, Department of Urology , Rigshospitalet, University of Copenhagen , Copenhagen , Denmark.

2

b Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences , King's College London , London , UK.

3

c Regional Cancer Centre Uppsala Örebro , Uppsala University Hospital , Uppsala , Sweden.

4

d CLINTEC-department , Karolinska Institutet , Stockholm , Sweden.

5

e Unit of Epidemiology , Institute of Environmental Medicine, Karolinska Institutet , Stockholm , Sweden.

6

f Medical Evidence and Observational Research, Global Medicines Development , AstraZeneca , Stockholm , Sweden.

7

g Department of Surgical Sciences , Uppsala University Hospital , Uppsala , Sweden.

Abstract

BACKGROUND:

In randomised controlled trials, men with advanced, non-metastatic prostate cancer (PCa) treated with anti-androgen monotherapy (AA) had similar all-cause mortality as men treated with gonadotropin-releasing hormone (GnRH) agonists. Using real-world evidence (i.e., observational data), we aimed to further assess the difference in mortality between these two drug categories.

MATERIAL AND METHODS:

We emulated a trial using data from Prostate Cancer data Base Sweden 3.0. We specifically focused on men diagnosed in 2006-2012 with high-risk PCa who had no distant metastasis. They either received primary hormonal therapy with AA (n = 2078) or GnRH agonists (n = 4878) who were followed for a median time of 5 years. Risk of death from PCa and other causes was assessed using competing risk analyses and Cox proportional hazards regression analyses, including propensity score matching.

RESULTS:

The cumulative 5-year PCa mortality was lower for men treated with AA (16% [95% confidence interval, CI, 15-18%]) than men treated with GnRH agonists (22% [95% CI 21-24%]). The 5-year other cause mortality was also lower for men on AA (17% [95% CI 15-19%] compared to men on GnRH agonists (27% [95% CI 25-28%]). In regression analyses, the risk of PCa death was similar, GnRH agonists versus AA (reference), hazard ratio (HR) 1.08 (95% CI 0.95-1.23), but the risk of death from all causes was higher for men on GnRH agonists, HR 1.23 (95% CI 1.13-1.34). Consistent results were seen in the propensity score-matched cohort.

CONCLUSION:

Our results indicate that the use of AA as primary hormonal therapy in men with high-risk non-metastatic PCa does not increase PCa-specific mortality compared to GnRH. Using AA instead of GnRH agonists may result in shorter time on/exposure to GnRH-treatment, which may reduce the risk of adverse events associated with this treatment.

PMID: 30375907 DOI: 10.1080/0284186X.2018.1529427

[pjoshea13]

You asked:

"What is the fundamental difference between "anti-androgen monotherapy (AA)" and "gonadotropin-releasing hormone (GnRH) agonists". It isn't so clear to me."

Let's suppose the comparison is between Casodex alone & Lupron alone. With Lupron, PCa is denied access to androgen via chemical castration. With Casodex alone, T levels remain normal but are prevented from activating the androgen receptor [AR].

In this population, there was a survival advantage in using AA monotherapy.

Of course, this paper comes at a time when there is great interest in aggressive treatment for these non-metastatic men - not monotherapy.

-Patrick

[AlanMeyer in reply to pjoshea13]

One consideration here is the power of the drugs.

Abiraterone acetate (Zytiga) is presumably more powerful than Lupron.

Enzalutamide (Xtandi) is presumably more powerful than Casodex.

The abstract didn't say what they used. However, as you say, today "... there is great interest in aggressive treatment for these non-metastatic men - not monotherapy"

Alan

[dbrooks_h in reply to pjoshea13]

Patrick, My first ADT treatment in 2006 was a Vantas Implant using the drug Histrelin, do you know if it would be more like lupron or casodex. It moved my psa level from 9 to undetectable in less than 3 months. The Eligard that I've been on for the last 2 years has not lower it all, seems to be stuck on 1, + or - .3 ( .8 to 1.3).

[pjoshea13 in reply to dbrooks_h]

Histrelin "is considered a gonadotropin-releasing hormone agonist or GnRH agonist." [1]

It "is a nonapeptide analogue of gonadotropin-releasing hormone (GnRH) with added potency."

So it is akin to Lupron. Eligard is Lupron.

-Patrick

[1] en.wikipedia.org/wiki/Histr...

[GP24]

Thank you for posting! I want to point out that non-metastatic in this study meant "no distant metastasis". They included patients with N0 and N1 while most were NX.

So according to this study you can use Bicalutamide/Casodex monotherapy if you have lymph node mets in the pelvis.

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