ADT/ARPI Suspension Displays Feasibility in Responders With Metastatic HSPC

Findings from the phase 2 A-DREAM/A032101 trial (NCT05241860) revealed that suspension of androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs) among responders may be feasible among patients with metastatic hormone-sensitive prostate cancer (HSPC), according to a presentation given at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO).¹

Among 78 responders to ADT plus ARPI treatment who underwent a treatment suspension, 45 (57.7%) remained treatment free for 18 months, 32 (41.0%) of whom also experienced testosterone recovery. Moreover, 52 patients (66.7%) experienced testosterone recovery regardless of treatment-free status by 18 months.

After a median follow-up of 26.9 months, 38.5% of patients remained off treatment (80% CI, 33.1%-48.9%; P = .0249). Moreover, 37.2% resumed ADT plus initial ARPI after meeting resumption criteria per protocol, with a further 6.4% continuing treatment prior to meeting resumption criteria. Additionally, 7.7% of patients withdrew from the study protocol before starting another treatment, with 1 (1.3%) reported death prior to subsequent treatment occurring due to prostate cancer. Non-protocol treatment was initiated by 7 (9.0%) patients, with 4 undergoing radiotherapy (5.1%), 2 (2.6%) undergoing a different ARPI, and 1 (1.3%) switching to a carboplatin/etoposide-based regimen.

The median duration off treatment was 24.5 months (95% CI, 19.3-not evaluable [NE]) in this group. Additionally, subgroup analyses showed that higher volume disease was associated with a higher likelihood of requiring subsequent cancer-directed therapy (HR, 3.05; 95% CI, 1.60-5.81); receipt of radiation to metastatic sites was associated with a lower likelihood of requiring subsequent therapy after treatment interruption (HR, 0.42; 0.18-0.94).

The radiographic progression-free survival (rPFS) and overall survival (OS) data were immature at the time of the analysis. The 24-month rates were 80.7% (95% CI, 71.5%-91.1%) and 95.0% (95% CI, 91.7%-100.0%), respectively.

“[The A-DREAM/A032101] study met its primary end point with 41% of patients…remaining treatment free with testosterone recovery 18 months after stopping ADT and ARPI,” Atish D. Choudhury, MD, PhD, chair of the Gelb Center for Translational Research and senior physician at the Dana-Farber Cancer Institute, as well as an assistant professor of medicine at Harvard Medical School, stated in the presentation. “[Additionally,] 38.5% of the patients continue on treatment interruption at a median of 26.9 months of follow-up. Only 1 of the 4 deaths that we have observed on the study have been from prostate cancer.”

Patients who were metastatic androgen pathway modulator sensitive on ADT and ARPI therapy, those with a prostate-specific antigen (PSA) level of less than 0.2 ng/mL, and those who received between 18 and 24 months of ADT and at least 12 months of ARPI were among those eligible to undergo the study protocol. Those enrolled underwent PSA or testosterone testing every 3 months, with scans and quality-of-life (QOL) assessments occurring every 6 months. Treatment re-initiation triggers included a PSA of 5 ng/mL, a radiographic change per Prostate Cancer Working Group 3 (PCWG3) criteria, and prostate cancer-related symptoms.

The median age on the study was 70 years (range, 49-90), and the majority of patients were White (84.6%) and non-Hispanic/Latino (88.5%). The median serum PSA prior to ADT/ARPI was 18.99 ng/mL (range, 5.04-6759.00), and 35.1% of patients had high volume CHAARTED status. A total of 39.7% did not receive prior therapy, with a further 70.5% not having received radiation to metastatic sites. Radiation as local therapy was administered in 51.3% of patients; 9.0% received a prostatectomy with or without radiation.

The primary end point of the analysis was 18-month treatment-free survival. Secondary end points included time to eugonadal testosterone, duration off symptoms, and QOL. Exploratory end points included rPFS, time to next treatment, OS––including cancer- and non–cancer-specific survival––and cost.

Reference

Choudhury AD, Ballman KV, Reimers MA, et al. 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). J Clin Oncol. 2026;44(suppl 16):5004. doi:10.1200/JCO.2026.44.16_suppl.5004