In an analysis from the phase III ARASENS trial reported in the Journal of Clinical Oncology, Maha Hussain, MD, FACP, FASCO, and colleagues found that the addition of darolutamide to androgen-deprivation therapy (ADT) and docetaxel significantly improved overall survival in subgroups of patients with metastatic hormone-sensitive prostate cancer with high-volume and high-risk disease.
The trial supported the August 2022 approval of darolutamide in combination with docetaxel in patients with metastatic hormone-sensitive prostate cancer receiving ADT.
Maha Hussain, MD, FACP, FASCO
Study Details
In the double-blind trial, 1,305 patients from sites in 23 countries were randomly assigned between November 2016 and June 2018 to receive darolutamide (n = 651) or placebo (n = 654) in combination with ADT and docetaxel. As previously reported, in the total population, the darolutamide group had significantly prolonged overall survival vs the control group (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.57–0.80, P < .0001). The current analysis assessed survival outcomes in subgroups with high-volume and high-risk disease.
High-volume disease was defined as visceral metastases and/or four or more bone metastases with at least one beyond the vertebral column/pelvis. High-risk disease was defined as two or more risk factors from among Gleason score ≥ 8, three or more bone lesions, and presence of measurable visceral metastases.
Key Findings
Among the total of 1,305 patients, 1,005 (77%) had high-volume disease, including 497 in the darolutamide group and 508 in the control group. The remaining 300 patients in the low-volume subgroup included 154 and 146 patients, respectively. A total of 912 patients (70%) had high-risk disease, including 452 and 460 patients, respectively. The remaining 393 patients in the low-risk subgroup included 199 and 194 patients, respectively.
Among patients with high-volume disease, median overall survival was not estimable (95% CI = 50.3 months to not estimable) in the darolutamide group vs 42.4 months (95% CI = 39.7–46.0 months) in the control group (HR = 0.69, 95% CI = 0.57–0.82). In the low-volume subgroup, median overall survival was not estimable (95% CI = not estimable to not estimable) in the darolutamide group vs not estimable (95% CI = not estimable to not estimable) in the control group (HR = 0.68, 95% CI = 0.41–1.13).
Among patients with high-risk disease, median overall survival was not estimable (95% CI = not estimable to not estimable) in the darolutamide group vs 43.2 months (95% CI = 40.0–48.9 months) in the control group (HR = 0.71, 95% CI = 0.58–0.86). In the low-risk subgroup, median overall survival was not estimable (95% CI = not estimable to not estimable) in the darolutamide group vs not estimable (95% CI = not estimable to not estimable) in the control group (HR = 0.62, 95% CI = 0.42–0.90).
The darolutamide group had prolonged time to castration resistance vs the control group among patients with high-volume disease (HR = 0.41, 95% CI = 0.34–0.49), low-volume disease (HR = 0.21, 95% CI = 0.14–0.33), high-risk disease (HR = 0.38, 95% CI = 0.32–0.46) and low-risk disease (HR = 0.32, 95% CI = 0.23–0.45).
Grade 3 or 4 adverse events occurred in 64.9% of patients in the darolutamide group vs 64.2% of the control group among patients with high-volume disease and in 70.1% vs 61.1% among those with low-volume disease. As noted by the investigators, “Among the most common adverse events, many were known toxicities related to docetaxel.”
The investigators concluded, “In patients with high-volume and high-risk/low-risk metastatic hormone-sensitive prostate cancer, treatment intensification with darolutamide, ADT, and docetaxel increased overall survival with a similar adverse event profile in the subgroups, consistent with the overall population.”
Dr. Hussain, of the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bayer AG and Orion Pharma. For full disclosures of the study authors, visit ascopubs.org.
