Atish Choudhury, MD, PhD, highlights phase 2 data on treatment interruption in mHSPC

In this video, Atish D. Choudhury, MD, PhD, discusses findings from the phase 2 A-DREAM / Alliance A032101 trial (NCT05241860) evaluating treatment interruption following favorable response to combination androgen deprivation therapy (ADT) and androgen receptor pathway inhibitor (ARPI) therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC).¹ These results were presented at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

Choudhury is a medical oncologist at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts.

Patients with mHSPC typically remain on continuous testosterone suppression, but prolonged treatment is associated with cumulative adverse effects, including sexual dysfunction, hot flashes, fatigue, and mood changes. Choudhury explained that although prior studies of intermittent hormonal therapy produced mixed results, they predated the routine use of intensified treatment with ADT plus an ARPI, which achieves deeper and more durable responses. Investigators therefore sought to determine whether patients with excellent responses to modern combination therapy could safely experience meaningful treatment-free intervals with testosterone recovery.

The single-arm phase 2 trial enrolled patients with mHSPC who had received ADT for 540 to 750 days and an ARPI for at least 360 days and achieved a prostate-specific antigen (PSA) level below 0.2 ng/mL at enrollment. After discontinuing both therapies, patients underwent PSA and testosterone monitoring every 3 months, imaging at least every 6 months, and resumed treatment if prespecified criteria—including PSA elevation to at least 5 ng/mL, radiographic progression, or prostate cancer-related symptoms—were met. The primary end point was the proportion of patients who remained treatment-free with recovery of eugonadal testosterone 18 months after treatment interruption.

According to Choudhury, the study met its primary objective, with 41% of patients remaining treatment-free with testosterone recovery at 18 months following treatment interruption (80% CI, 33.5 to 48.9; one-sided P = .0249). At a median follow-up of 21.2 months, 35% of patients had resumed their original ADT-plus-ARPI regimen after meeting protocol-defined criteria, while additional patients either resumed treatment earlier (5%), pursued alternative therapies (9%), or withdrew from the study (5%). Choudhury noted that the proportion of patients who remained off all cancer-directed therapy exceeded expectations, suggesting that carefully selected patients who achieve deep responses to combination hormonal therapy may be candidates for extended treatment breaks. Ongoing analyses will evaluate biomarkers, patient-reported outcomes, and long-term clinical outcomes to better define which patients may benefit most from this approach.

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