Yesterday, when I complained of the apparent lack of interest in using BAT to prevent CRPC, I should have briefly mentioned the old BATMAN study (2016).
Although BATMAN involved hormone-sensitive men, there was no castration phase. Therefore, the BATMAN protocol was not designed to prevent CRPC.
Michael Schweizer was the lead author, although he had already moved on to Fred Hutchinson in Seattle. The other 11, including Denmeade were at Johns Hopkins.
BATMAN was a Phase II study where 29 "patients received BAT following the {6 month} ADT lead-in."
Comment: why such a long lead-in? The aim seems to have been to ensure a starting PSA of <4 ng/mL.
"The primary endpoint was the percent of patients with a PSA <4 ng/ml after 18 months. "
Comment: the PSA start & end point of <4 ng/mL seems spurious. What they are aiming for is an 18 month period ending with a PSA that has never increased beyond the start point.
The men "receive{d} alternating 3-month cycles of BAT and ADT. BAT was administered as intramuscular testosterone (T) cypionate or enanthate 400 mg on Days (D) 1, 29, and 57."
Comment: notice the sleight of hand? It's a classic 28-day BAT cycle. The significance of the 3-months presumably being that the men had to remain below 4 ng/mL by the end of each 3 months in order to continue for another 3 months.
"The primary endpoint was met, with 17/29 men (59% ...) having a PSA <4 ng/ml at 18 months."
Comment: it appears that BAT did not work for 41% of the men. However ...
Note that: "ADT was continued throughout the study to allow rapid cycling from near castrate to supraphysiologic range T following T injections."
There was no castrate phase! "ADT" is a red herring, in that there is no meaningful use of castration. I know from experience that testosterone cypionate injected into thigh muscle lingers. It fades away slowly. By the time that it has entirely disappeared, it is almost time for another T-cyp shot. 28 days is a very short cycle; clearance rates will vary. One month of castrate levels following the wash-out would have been much more interesting.
What BATMAN tried to do is to use oscillating testosterone levels to manage PCa. The use of ADT being a gimmick to produce a right-hand-side testosterone sine curve. Denmeade had a 6-year follow-up paper this month [2].
I'm not particularly interested in the findings, except as they relate to responders. "Median {overall survival is not reached} for responders ...", but see below if you want more.
-Patrick
[1] pubmed.ncbi.nlm.nih.gov/273...
[2] pubmed.ncbi.nlm.nih.gov/359...
Results: Over median follow-up of 95 months, the median PFS on ADT for the entire cohort was 47.8. Median OS has not been reached (NR). Median OS for Non-Responders is 43 months versus NR (not reached) for responders (hazard ratio [HR]: 0.176, p = 0.002). Post-BAT, the PSA50 and PSA90 responses to abiraterone or enzalutamide were 94.4% and 66.7%, respectively and median PFS was 20.6 months. Patients with peak PSA level of ≥9 ng/ml after BAT had median PFS of 20.6 months versus NR for those having PSA < 9 ng/ml (HR: 0.122, p < 0.001). Median OS was 79.6 months for patients with PSA peak of ≥9 ng/ml versus NR for those having PSA peak of <9 ng/ml (HR: 0.409, p = 0.131).
