Darolutamide Monotherapy Lowers PSA in Patients With Hormone-Sensitive Prostate Cancer
Darolutamide monotherapy resulted in a reduction in prostate-specific antigen response by ≥ 80% in all evaluable patients with hormone-sensitive prostate cancer while maintaining testosterone levels, according to the results of a recent 24-week randomized study.
The phase 2 study evaluated the efficacy and safety of darolutamide monotherapy in patients with hormone-sensitive prostate cancer (PCa) who maintained eugonadal testosterone levels. Unlike conventional androgen deprivation therapy (ADT), darolutamide, a novel androgen receptor inhibitor, does not suppress testosterone levels, potentially offering an alternative therapeutic approach.
This 24-week, open-label, randomized trial enrolled 61 men with histologically confirmed PCa requiring gonadotropin-releasing hormone (GnRH) therapy. Participants were randomized to receive darolutamide (600 mg bid) or a commercially available GnRH analog, with the latter serving as an internal control.
The study’s primary endpoint was a prostate-specific antigen (PSA) response, defined as a ≥ 80% decline in PSA levels from baseline to week 24. Secondary endpoints included changes in testosterone levels, safety, tolerability, and quality of life metrics.
Among the 23 evaluable patients in the darolutamide arm, 100% achieved the primary endpoint, demonstrating a median PSA decline of – 99.1%. Notably, serum testosterone levels increased by a median of 44.3%, whereas patients in the GnRH arm experienced a significant decline in testosterone levels. In terms of safety, 48.4% of patients on darolutamide reported treatment-related adverse events (AEs), primarily grade 1 or 2, with gynecomastia (35.5%), fatigue (12.9%), hot flashes (12.9%), and hypertension (12.9%) being the most common.
Study limitations included a relatively small sample size and early termination due to slow recruitment. Furthermore, the absence of long-term follow-up precludes conclusions regarding the durability of PSA suppression and overall survival benefits.
“We demonstrated that treatment with darolutamide as monotherapy induces a significant PSA response in nearly all men with hormone-naïve PCa,” the study authors concluded.
Reference
Tombal BF, Gomez-Veiga F, Gomez-Ferrer A, et al. A phase 2 randomized open-label study of oral darolutamide monotherapy versus androgen deprivation therapy in men with hormone-sensitive prostate cancer (EORTC-GUCG 1532). Eur Urol Oncol. 2024;7(5):1051-1060. doi:10.1016/j.euo.2024.01.009