A-DREAM Trial Suggests Some Men with Metastatic Prostate Cancer May Stop Therapy Safely for a Time

A new phase 2 study, A-DREAM / Alliance A032101, suggests that a carefully selected group of men with metastatic hormone-sensitive prostate cancer may be able to interrupt androgen deprivation therapy and an androgen receptor pathway inhibitor after achieving an excellent response, while still maintaining a treatment-free interval. The study met its primary endpoint, with 41% of participants remaining off treatment and having recovered testosterone 18 months after interruption.

The trial focused on a highly selected population. Eligible patients had metastatic hormone-sensitive prostate cancer on conventional imaging, a PSA of at least 5 ng/mL and testosterone of at least 150 ng/dL before treatment, and then achieved PSA below 0.2 ng/mL and testosterone below 50 ng/dL after receiving androgen suppression for 540 to 750 days and an ARPI for at least 360 days. Prior local therapy, radiation to metastases, and docetaxel were allowed.

After enrollment, patients stopped both testosterone suppression and the ARPI and were monitored regularly with PSA, testosterone, imaging, and patient-reported outcomes. Treatment could be restarted if PSA rose to 5 ng/mL or higher, if imaging showed progression, or if prostate cancer symptoms appeared. At 18 months, 67% had recovered testosterone, 58% remained treatment-free, and 41% remained both treatment-free and eugonadal.

The headline result is encouraging because it suggests that treatment de-escalation is possible for a subset of men who respond exceptionally well to initial therapy. In practical terms, this could mean a meaningful break from ongoing hormonal treatment and potentially less toxicity, at least for some time. Still, the study is single-arm and relatively early, so it does not prove that interruption is better than continuous therapy for long-term cancer control.

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