Castration-resistant prostate cancer (CRPC) is a type of prostate cancer that keeps growing even when the testosterone level is reduced to very low. Darolutamide is a nonsteroidal androgen receptor (AR) antagonist with a molecular structure that differs from other AR antagonists. To date, darolutamide is neither approved by the European Medicines Agency (EMA) nor by the U.S. Food and Drug Administration (FDA) for any indication.

The ARAMIS trial aimed to investigate the efficacy and safety of darolutamide compared to placebo in men with nonmetastatic CRPC. The trial is currently ongoing; thus, presented data are primary- and interim results. The primary analysis of median metastasis-free survival (MFS) showed a gain of 22 months in patients who received darolutamide compared to patients who received placebo (hazard ratio [HR] for metastasis or death in the darolutamide group was 0.41). This beneficial treatment effect of darolutamide was observed across all pre-specified subgroups. An interim analysis of OS showed a lower risk of death with darolutamide as compared to placebo (HR for death was 0.71); however, median OS data have not been reached in either group. Progression-free survival (PFS, an exploratory endpoint) was statistically significantly longer (36.8 months) in patients in the darolutamide group than in patients in the placebo group (14.8 months). In patients receiving darolutamide, the time to pain progression and the time to prostate-specific antigen (PSA) progression were prolonged by 14.9 months and 25.9 months respectively. Health-related quality of life (HRQoL) and disease specific quality of life (QoL) were evaluated by the use of five different questionnaires. Overall, patient-reported QoL was similar between the two treatment groups.

The ARAMIS trial showed that darolutamide provides a prolongation of MFS in patients with nonmetastatic CRPC and was associated with better outcomes regarding disease progression than in patients in the placebo group. However, the presented data are from the primary and interim analyses; final results of all endpoints are lacking. Hence, the actual clinical benefit of darolutamide is not yet proven. In this regard, more data concerning efficacy, safety and long-term results is required, as well as a direct comparison with other AR antagonists to determine the optimal treatment for affected patients. Darolutamide is currently not approved, but may provide an additional treatment option for patients with nonmetastatic CRPC.