ARASTEP: Targeting High-Risk Biochemical Recurrence in Prostate Cancer

In an interview with Targeted Oncology^TM, Alicia Morgans, MD, MPH, genitourinary medical oncologist at Dana-Farber Cancer Center in Boston, Massachusetts, discusses the phase 3 ARASTEP study (NCT05794906) presented as a trial in progress at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

The ARASTEP trial is an international phase 3 study focusing on patients with high-risk biochemical recurrence of prostate cancer. Traditionally, this has meant recurrence after primary treatment like radiation or prostatectomy. However, ARASTEP specifically selects patients whose high-risk recurrence is characterized by prostate-specific membrane antigen (PSMA) PET-positive metastatic disease.

In this trial, patients are randomized to receive either androgen deprivation therapy (ADT) for 2 years or ADT combined with darolutamide (Nubeqa) for 2 years. Importantly, physicians can also recommend metastasis-directed radiation to all PSMA PET-positive areas.

The rationale for including darolutamide is strong, according to Morgans. Androgen receptor pathway inhibitors have improved outcomes in various prostate cancer settings. These studies consistently demonstrate the significant benefits of targeting the androgen receptor.

The primary hope with ARASTEP is to prolong the time to PSMA PET progression. This is a groundbreaking end point from a regulatory perspective, according to Morgans, as it hasn't been used before. It offers an exciting opportunity for the prostate cancer field to better understand the correlation between PSMA PET progression and other crucial outcomes, such as metastasis-free survival by conventional imaging (a key secondary end point) and overall survival (a standard secondary end point in advanced prostate cancer studies).

Ultimately, ARASTEP aims to understand how a defined duration of systemic and metastasis-directed therapy can truly prolong the time to next therapy or even negate the need for further treatment in patients with relapsed disease. This is a very important approach for managing recurrent prostate cancer.

“Our understanding of how we can use that sort of finite duration of systemic therapy, metastasis, directed therapy, and try to really prolong or even negate the need prolong the time to next therapy or negate the need for another therapy, is, I think, a really important approach to patients with relapsed disease,” Morgans said in the interview.