BAT & Abiraterone / Enzalutamide resensitization

[pjoshea13]

BAT is bipolar androgen therapy. Men receive cyclic high-dose testosterone injections while on ADT.

IMO, BAT is best started along with ADT because it may delay CRPC indefinitely.

There are numerous reasons for CRPC & not everyone will respond to BAT at that stage - particularly in heavily treated Abiraterone [Abi] & Enzalutamide [Enza] cohorts after resistance to those drugs.

38% of the post-Abi group experienced PSA reduction although only 17% achieved a 50% or more reduction. The median number of BAT cycles (28 days) was 5, with a range of 1 to 25. In those who went on to an Abi rechallenge, 16% had a PSA reduction of 50% or more.

The post-Enza experience was much better. 30% (versus 17%) achieved a 50% or more PSA reduction. 68% (versus 16%) had a PSA reduction of 50% or more during the Enza rechallenge.

The median 'clinical or radiographic progression-free survival (crPFS)' was also better - 6 months versus 4 months.

"The median time from enrollment to progression following rechallenge with AR-targeted therapy (ie, progression-free survival 2; PFS2) was longer in the post-enzalutamide versus post-abiraterone patients (12.8 vs 8.1 mo ...)"

Certainly worth trying IMO.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/326...

Eur Urol

. 2020 Jul 2;S0302-2838(20)30471-1. doi: 10.1016/j.eururo.2020.06.042. Online ahead of print.

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

Mark C Markowski 1 , Hao Wang 2 , Rana Sullivan 3 , Irina Rifkind 3 , Victoria Sinibaldi 3 , Michael T Schweizer 4 , Benjamin A Teply 5 , Nduku Ngomba 3 , Wei Fu 2 , Michael A Carducci 3 , Channing J Paller 3 , Catherine H Marshall 3 , Mario A Eisenberger 3 , Jun Luo 6 , Emmanuel S Antonarakis 3 , Samuel R Denmeade 3

Affiliations expand

PMID: 32624280 DOI: 10.1016/j.eururo.2020.06.042

Abstract

Background: Cyclic high-dose testosterone injections, also known as bipolar androgen therapy (BAT), is a novel treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). BAT has shown clinical activity in prior studies enrolling men with mCRPC and may potentially restore sensitivity to prior androgen receptor (AR)-targeted agents.

Objective: To evaluate the clinical activity of BAT in patients progressing on AR-targeted therapy as well as responses to abiraterone or enzalutamide upon rechallenge after BAT.

Design, setting, and participants: RESTORE is a multicohort phase II study enrolling asymptomatic mCRPC patients after abiraterone or enzalutamide at Johns Hopkins Hospital (NCT02090114). Participants (29 after abiraterone and 30 after enzalutamide) received 400 mg testosterone cypionate intramuscularly every 28 days, with ongoing luteinizing hormone-releasing hormone agonist/antagonist treatment (ie, BAT). Following progression on BAT, patients were rechallenged with their most recent AR-targeted therapy.

Outcome measurements and statistical analysis: Coprimary endpoints were >50% decline in PSA from baseline (PSA50) responses to BAT and following AR-targeted therapy rechallenge. Outcomes in the post-abiraterone cohort are presented, as well as updated results from the post-enzalutamide cohort and an exploratory AR-V7 analysis.

Results and limitations: No statistically significant difference in PSA50 response rates to BAT was observed (30% [post-enzalutamide cohort] vs 17% [post-abiraterone cohort], p = 0.4). However, PSA50 responses to AR-targeted therapy rechallenge were higher in the post-enzalutamide cohort (68% vs 16%, p = 0.001). The median time from enrollment to progression following rechallenge with AR-targeted therapy (ie, progression-free survival 2; PFS2) was longer in the post-enzalutamide versus post-abiraterone patients (12.8 vs 8.1 mo, p = 0.04). Outcomes were worse in patients with detectable AR-V7 in circulating tumor cells (median PFS2: 10.3 vs 7.1 mo, p = 0.005).

Conclusions: BAT shows clinical activity in mCRPC patients and may be more effective at resensitizing to enzalutamide versus abiraterone.

Patient summary: BAT is well tolerated in metastatic castration-resistant prostate cancer patients. The type of prior AR-targeted therapy might affect response to BAT as well as AR-therapy rechallenge. BAT followed by AR-targeted therapy rechallenge did not improve outcomes in AR-V7-positive patients.

Keywords: Androgen receptor–targeted therapy; Bipolar androgen therapy; Testosterone.

Copyright © 2020. Published by Elsevier B.V.

[cesces]

"There are numerous reasons for CRPC & not everyone will respond to BAT at that stage - particularly in heavily treated Abiraterone [Abi] & Enzalutamide [Enza] cohorts after resistance to those drugs."

Interesting. That would mean BAT should be considered as a very early option?

[Fairwind]

Since BAT is not "Standard of Care" nor is it FDA approved..Therefore, obtaining BAT is VERY difficult outside a clinical trial...Also, it is not without it's side-effects..There is a poster on this board who is doing D.I.Y. BAT using testosterone "obtained through other channels.."

[Shanti1]

I agree that BAT started along with ADT may turn out to prolong the hormone-sensitive stage. I would certainly be interested if anyone knows of any studies or clinical trials, or if anyone is actively trying this.

[kaptank]

"BAT followed by AR-targeted therapy rechallenge did not improve outcomes in AR-V7-positive patients."

That is puzzling as early work by the Johns Hopkins teams indicated that supraT "turned off" ARV7 (ie ARV7+ became ARV7-) and was one of the several routes by which antiandrogen sensitivity was restored.

We are still a long way from fully understanding the optimal use of BAT. I agree it would be useful to know if the occasional shot of supra T extends ADT from the very start.

[AlanLawrenson]

I came across about 6 or 7 papers on this topic when rearching BAT for my latest PCa book. An ABC of Prostate Cancer Today - 3rd Edition. It includes a page or two on this treatment.

[Walkingwell]

useful, some things to think about, thanks

[Chask]

My MO very nervous about BAT, especially after Abiraterone. I have raised the question, but he is not happy about filling me up with Testosterone. Can’t say Abi has failed, but PSA is rising, albeit very slowly.

[EdBar]

Dr. Sartor has this option on the table for me if/when Xtandi fails, he is one of the MO’s who use this to rechallenge Xtandi.

Ed

[tarhoosier]

I have a friend who is 16+ years in, and he exhausted lupron, then had orchiectomy, then xtandi and then then docetaxel and then a rising psa on treatment. He convinced his VA doctor to try BAT and had an 8-9 month decline in psa. He rechalllenged with Xtandi and psa went from 13 to 6 in the past two months and he intends to ride this cycle as long as possible. VA doctor is treating him as a lab rat for trial of n=1.