Dr Choudhury on the Evaluation of Treatment Interruption After Response in mHSPC

Atish D. Choudhury, MD, PhD, senior physician, chair, Gelb Center for Translational Research, Dana-Farber Cancer Center, assistant professor of medicine, Harvard Medical School, discusses the rationale and methodology behind the phase 2 A-DREAM trial (NCT05241860) investigating the potential for interrupting treatment in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who show exceptional responses to initial therapy combining androgen deprivation therapy (ADT) and a novel androgen receptor (AR) pathway inhibitor.

An overview of the ongoing trial was detailed at the 2024 ASCO Annual Meeting, and Choudhary explains that the study is including patients with mHSPC who have been receiving ADT for 18 to 24 months and an AR inhibitor for at least 12 months. Patients are allowed to enrolle if they have a stable or falling prostate-specific antigen (PSA) level below 0.2 ng/mL and a castrate testosterone level under 50 ng/dL at baseline after having a PSA level of at least 5 ng/mL and a testosterone level of at least 150 ng/dL prior to the start of ADT. Those eligible for enrollment then discontinue treatment with both ADT and the AR pathway inhibitor. They are monitored and retested for PSA once every 3 months and scans every 6 months, Choudhary says.

Patients can re-initiate treatment of their PSA levels rise to at least 5 ng/mL, they have a radiographic change in their prostate cancer, or they experienced symptoms attributed to prostate cancer.

The primary end point of the trial is to assess the proportion of patients who remain treatment-free at 18 months with eugonadal testosterone levels over 150 ng/dL. Secondary outcomes include the time to return to eugonadal testosterone levels, duration off treatment, and variations in patient-reported outcomes regarding quality of life (QOL). Exploratory objectives include radiographic progression-free survival, time to next treatment, overall survival, and the correlation of specific tissue- and blood-based biomarkers with clinical endpoints.

This ongoing trial seeks to redefine management strategies for mHSPC by integrating periods of treatment interruption based on robust initial responses with the goal of improving QOL without affecting treatment outcomes.