Why are patients getting enzalutamide s/p prostatectomy not candidates for salvage radiation therapy?

Although there have been other efforts to profile the role of enzalutamide (e.g., SALV-ENZA, Tran et al., PMID 36367998) or other second generation androgen axis inhibitors (e.g., FORMULA-509) in conjunction with salvage RT, EMBARK (Freedland et al., PMID 38320501) was designed to test the efficacy (and safety) of enzalutamide (± leuprolide) as compared with leuprolide monotherapy in patients with biochemical recurrence (BCR) who were without curative treatment options. Thus, patients were excluded if they were felt to be candidates for salvage RT (SRT) at trial screening, as SRT is potentially curative.

There were, however, patients potentially eligible for SRT who were included. Approximately one-third of the patients enrolled with a hist...

I’ve asked this question to people on the EMBARK trial as well as reps and presenters, since it came out.

I very rarely use EMBARK. The main problem was the lack of PET. The study quoted above for the "EMBARK-like" cohort at UCLA supports my practice pattern.

I will, however, discuss EMBARK with patients who are close or at “EMBARK-like” criteria. These are men with serial negative PET, rising PSA, and falling doubling time, mainly to help assuage anxiety. I have not had a single patient actually take enza in this scenario.

Also, I do not think the biggest side effect of enza is gynecomastia, which happens with monotherapy. The biggest side effects are fatigue and mental dulling from blood-brain penetration, it can be profound, extreme, and p...