What question did this study set out to answer?

This trial aims to determine if treatment interruption in responding patients can lead to prolonged treatment-free periods with testosterone recovery.

May 29, 2026

A phase 2 trial of androgen deprivation therapy interruption in patients responding exceptionally to androgen receptor pathway inhibitor in metastatic hormone-sensitive prostate cancer (A-DREAM / Alliance A032101).

Key Points

This trial aims to determine if treatment interruption in responding patients can lead to prolonged treatment-free periods with testosterone recovery.
Single-arm phase 2 trial (NCT05241860) with 78 eligible patients with metastatic hormone-sensitive prostate cancer.
Patients underwent treatment interruption after achieving low PSA and testosterone levels, followed for outcomes like PSA and testosterone every 3 months.
Evaluated primary endpoint of patients remaining treatment-free with eugonadal testosterone at 18 months post-interruption.
By 18 months after treatment interruption, 41% of patients (32/78) maintained treatment-free status with testosterone recovery (80% CI 33.5-48.9%, one-sided p 0.0249).
67% of patients (52/78) achieved testosterone recovery.
At median follow-up of 21.2 months, 35% of patients (27/78) resumed treatment after meeting re-initiation criteria.

Abstract

5004 Background: Patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated continuously with testosterone suppression (TS) plus an androgen receptor pathway inhibitor (ARPI) can experience cumulative toxicity. We conducted this single-arm phase 2 trial (NCT05241860) to test the hypothesis that pts who achieve favorable response to TS + ARPI can have prolonged treatment-free interval with testosterone recovery after treatment interruption (TI). Here we report on the primary endpoint. Methods: Eligible pts had mHSPC by conventional imaging with prostate-specific antigen (PSA) ≥ 5 ng/ml and testosterone ≥ 150 ng/dl prior to starting TS+ARPI, with PSA 150 ng/dl). Target enrollment was 75 pts to differentiate 18-mo treatment-free rates of 0.30 (H 0 ) and 0.45 (H a ). Results: Of 79 pts enrolled between 07/2022 and 03/2024, 78 were eligible and underwent TI. Among these 78, median PSA prior to starting TS+ARPI was 19 (range 5-6759), 27 (35%) had high volume disease, 31 (40%) never received local therapy, and 55 (71%) did not receive radiation to metastases. By 18 mo after TI, 67% (52/78) recovered testosterone and 58% (45/78) remained treatment-free; 41% (32/78) remained treatment-free with testosterone recovery (80% CI 33.5-48.9%, one-sided p 0.0249). At median follow-up of 21.2 mo, 35% (27/78) resumed initial TS+ARPI after meeting re-initiation criteria (of whom 1 required treatment switch for PD 9 mo later); 5% (4/78) resumed prior to meeting criteria; 9% (7/78) pursued alternative therapy instead of resuming TS+ARPI per protocol; 5% (4/78) withdrew; 1 died of myocardial infarction prior to resuming treatment. 4 pts died, 1 of prostate cancer. Conclusions: The primary objective was achieved with 41% of favorable responders to TS+ARPI remaining treatment-free with testosterone recovery at 18 mo after TI. Analyses of biomarkers and PROs are in progress, and pts will be followed for long-term outcomes. Support: U10CA180821, U10CA180882, UG1CA189823, https://acknowledgments.alliancefound.org, Veracyte Inc. Clinical trial information: NCT05241860 .

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