An international team of researchers have found that combining darolutamide with androgen-deprivation therapy and docetaxel improved overall survival in men with metastatic hormone sensitive prostate cancer.
Darolutamide is a potent androgen-receptor inhibitor which has been shown to improve survival in men with non-metastatic, castration-resistant prostate cancer when used alongside androgen-deprivation therapy. Furthermore, the ARASENS trial published in 2022 in the New England Journal of Medicine, found that in men with metastatic, hormone-sensitive prostate cancer, use of oral darolutamide (600 mg twice daily), androgen-deprivation therapy (ADT) and docetaxel (DOC) significantly improved overall survival compared to a placebo group without the drug but with both ADT and DOC.
In the current analysis, researchers undertook a post hoc analysis of ARASENS and focused on the effect of darolutamide in various subgroups. Participants were categorised into those with high-volume disease (defined by visceral metastases and or > 4 bone metastases with ≥ 1 beyond the vertebral column/pelvis) or high-risk disease, which was a Gleason score > 8 and > 3 bone lesions and the presence of visceral metastases. The team also investigated those with both low risk and low volume disease, i.e., not meeting the high volume/risk criteria. For their analysis the primary endpoint was set as overall survival.
Darolutamide and overall survival in subgroups
A total of 1,305 participants of whom 1,005 (77%) had high-volume disease and 912 (70%) high-risk disease were included in the analysis.
Treatment with darolutamide improved overall survival compared to placebo in those with high volume disease by 31% (hazard ratio, HR = 0.69, 95% CI 0.57 – 0.82) and by a similar amount in those with high-risk disease (HR – 0.71, 95% CI 0.58 – 0.86). There were also broadly similar improvements in overall survival among those with low volume and low risk disease.
In terms of safety, grade 3 or 4 adverse events occurred in a similar proportion of patients (64.9% vs 64.2% darolutamide vs placebo group) in the high volume subgroup and the incidence was similar across all subgroups.
The authors concluded that in men with hormone sensitive metastatic prostate cancer, treatment intensification with darolutamide, androgen-deprivation therapy, and docetaxel led to an increased OS and with a similar adverse effect profile in the subgroups.
Hussain M et al. 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. J Clin Oncol 2023