ARASAFE Trial Offers Safer Docetaxel-Darolutamide-ADT Regimen for mHSPC

Recent data presented at the 2025 European Society for Medical Oncology (ESMO) Congress reveal a promising new treatment schedule for patients with metastatic hormone-sensitive prostate cancer (mHSPC). The phase 3 ARASAFE trial evaluated an alternative docetaxel dosing regimen combined with darolutamide and androgen deprivation therapy (ADT), showing significant reductions in severe toxicities while maintaining effective cancer control.

Current standard care for mHSPC often includes triplet therapy with docetaxel (75 mg/m² every 3 weeks), darolutamide, and ADT. However, this regimen is associated with substantial high-grade adverse effects (AEs) such as neutropenia, which can limit treatment tolerability and patient quality of life. The ARASAFE trial hypothesized that a lower-dose, more frequent docetaxel schedule—50 mg/m² every 2 weeks—might alleviate these toxicities.

The randomized study enrolled 250 patients who received either the standard 75 mg/m² every 3 weeks or the alternative 50 mg/m² every 2 weeks docetaxel dosing, both alongside darolutamide and ADT. Despite the higher cumulative dose in the experimental arm (600 mg/m² versus 450 mg/m² in the standard arm), the ARASAFE regimen demonstrated a statistically and clinically significant reduction in grade 3 to 5 adverse events: 61.2% versus 78.9% in the standard arm (P = 0.0024). Notably, grade 3-4 neutropenia and death rates were dramatically lower, 24.0% versus 64.1% (P < 0.00001).

Secondary efficacy endpoints, including prostate-specific antigen (PSA) responses, time to castration resistance, overall survival, and quality of life measures, showed comparable oncologic outcomes between the groups, reinforcing the oncologic safety of the alternative dosing.

This improved safety profile without compromising efficacy positions the ARASAFE regimen as a potential new standard of care in mHSPC treatment.

Source.