The following is a summary of “Darolutamide Plus Androgen-Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase III ARASENS Trial,” published in the July 2023 issue of Oncology by Hussain, et al.

For a study, researchers sought to evaluate the efficacy and safety of darolutamide in the ARASENS trial across subgroups categorized by disease volume and risk in patients with metastatic hormone-sensitive prostate cancer.

In the study, patients diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) were enrolled and randomly assigned to two treatment groups: darolutamide or placebo. Both groups received androgen-deprivation therapy (ADT) and docetaxel. The high-volume disease was characterized by the presence of visceral metastases and/or ≥ 4 bone metastases, with ≥ 1 metastasis beyond the vertebral column/pelvis. On the other hand, high-risk disease was defined as meeting ≥ 2 risk factors, which included a Gleason score ≥ 8, ≥ 3 bone lesions, and the presence of measurable visceral metastases.

Out of the total 1,305 patients included in the study, 1,005 (77%) were identified as having high-volume disease, while 912 (70%) were classified as having high-risk disease. The administration of darolutamide demonstrated improved overall survival (OS) compared to placebo across various disease categories. In patients with high-volume disease, the hazard ratio (HR) for darolutamide was 0.69 (95% CI, 0.57 to 0.82), indicating a significant survival benefit. Similarly, in patients with high-risk disease, the HR for darolutamide was 0.71 (95% CI, 0.58 to 0.86), and in those with low-risk disease, the HR was 0.62 (95% CI, 0.42 to 0.90). Even in the smaller subgroup of patients with low-volume disease, there were indications of a survival benefit with darolutamide (HR, 0.68; 95% CI, 0.41 to 1.13). Darolutamide also showed improvements in secondary endpoints, such as time to castration-resistant prostate cancer and subsequent systemic antineoplastic therapy across all disease volume and risk subgroups. Adverse events (AEs) were similar between the treatment groups in all subgroups. Grade 3 or 4 AEs occurred in 64.9% of darolutamide-treated patients compared to 64.2% of placebo-treated patients in the high-volume subgroup, and in the low-volume subgroup, the respective percentages were 70.1% and 61.1%. Many of the common AEs observed were known toxicities associated with docetaxel.

Treatment intensification with darolutamide, androgen-deprivation therapy, and docetaxel resulted in increased overall survival with a comparable safety profile in patients with high-volume and high-risk/low-risk metastatic hormone-sensitive prostate cancer, consistent with the findings in the overall study population.

Source: ascopubs.org/doi/full/10.1200/JCO.23.00041