ARAMIS: Efficacy and Safety of Darolutamide in Nonmetastatic Castration-Resistant Prostate Cancer

For men with non-metastatic castrate resistant prostate cancer (nmCRPC) delaying the development of metastases while minimizing the risk of adverse events, is an important treatment goal.

At the recent ASCO GU conference, we learned the results from the ARAMUS phase III trial which evaluated Darolutamide, an androgen receptor (AR) antagonist (a drug that prevents androgens from affecting prostate and prostate cancer cells). The trial studied the efficacy and safety of darolutamide in men with nmCRPC men.

The trial was a double-blind, placebo-controlled phase III trial that randomized nmCRPC men in a 2:1 ratio to receive darolutamide 600 mg (two 300 mg tablets) twice daily or placebo, while they continued androgen deprivation therapy (ADT).

The primary endpoint of the trial was metastasis-free survival (MFS), with independent central review of radiographic imaging every 16 weeks. Secondary endpoints include overall survival (OS), time to pain progression first use of cytotoxic chemotherapy and first symptomatic skeletal event, as well as a safety profile.

The trial, which evaluated 1,509 men showed:

1- Median MFS was 40.4 months with darolutamide vs. 18.4 months with placebo.

2- Overall survival showed a trend in favor of darolutamide.

3- Time to pain progress also showed a trend in favor of darolutamide over placebo.

4- Other secondary and exploratory efficacy endpoints also favored darolutamide.

The noted incidences of treatment adverse events (AEs) and discontinuation of therapy were comparable between darolutamide and the placebo arms;

Conclusion: Among men with nmCRPC, metastasis-free survival was significantly longer with darolutamide than with placebo along with a low incidence of treatment-related adverse events.

Darolutamide is not approved by the FDA. For it to be considered for approval, the data will need to be submitted to the FDA. The other androgen receptor antagonists that are currently FDA approved in the same space are bicalutamide (Casodex), apalutamide (Erleada) and enzalutamide (Xtandi).

Clinical trial information: NCT02200614

Study Authors: Karim Fizazi, Neal D. Shore, et al.