Dr Grimm on the Rationale for Conducting a Post-Hoc Analysis of ARASENS in mHSPC

Marc-Oliver Grimm, MD, professor, chairman, Department of Urology, Jena University Hospital, discusses the rationale for conducting a post-hoc analysis of the phase 3 ARASENS trial (NCT02799602) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

The ARASENS trial was designed to evaluate the efficacy of a triplet therapy consisting of darolutamide, androgen deprivation therapy (ADT), and docetaxel in patients with mHSPC. This combination was compared with a control arm, in which patients received docetaxel plus ADT and a placebo, Grimm begins. The primary results from this trial demonstrated a significant reduction in the risk of death for the triplet therapy group vs the placebo group, he reports.

The rationale behind the post-hoc analysis of the ARASENS trial was to gain insights into the treatments patients received after their disease progressed and how these treatments influenced their outcomes, Grimm says. Specifically, the analysis focused on the differences in post-progression therapies that these patients received. It was found that patients who received the triplet therapy had no difference in post-progression survival regardless of whether they were subsequently treated with an androgen receptor pathway inhibitor (ARPI) or non-ARPI treatments, he elucidates. However, these patients experienced rapid progression on subsequent therapies after receiving the initial triplet combination, Grimm states. Despite this, the significant advantage was that these patients remained in the mHSPC stage for a longer duration, which is associated with a better quality of life, minimal pain, and delayed progression, according to Grimm.

In the placebo group, patients who progressed and were treated with ARPI therapies, such as abiraterone acetate (Zytiga) or enzalutamide (Xtandi), had better outcomes compared with those treated with non-ARPI therapies, such as docetaxel or cabazitaxel (Jevtana), he expands. This finding highlights the potential benefits of ARPI treatments in extending survival post-progression for patients initially treated with ADT and docetaxel, he concludes.