Darolutamide plus androgen-deprivation therapy: propensity score matching of ARASEC and historic clinical trial patients.

Darolutamide plus androgen-deprivation therapy (ADT) with docetaxel is one of the standards of care for metastatic hormone-sensitive prostate cancer (mHSPC), based on the phase III ARASENS study. To provide the option to use darolutamide without docetaxel to meet patients' needs and preferences, the phase III placebo-controlled ARANOTE study was undertaken. Reflecting evolving treatment guidelines for mHSPC, the complementary US-based ARASEC study was designed with a single, prospectively-enrolled investigational arm (darolutamide plus ADT) and an ADT monotherapy arm derived from the previous phase III CHAARTED study. ARASEC was designed with the same eligibility criteria and assessments as CHAARTED, and patients were matched 1:1 using propensity scores calculated from key prognostic baseline variables: age, ECOG performance status, extent of disease, prior local therapy, Gleason score, and prostate-specific antigen level. ARASEC enrolled 223 patients who received darolutamide plus ADT, with 393 patients in the CHAARTED ADT control arm available for matching. Matching yielded 160 patients in each arm with minimal differences in prognostic variables between the matched groups, who will be compared to evaluate the efficacy and safety of darolutamide plus ADT in mHSPC. This novel study design may inform future single-arm trials with historical control arms, with potentially faster accrual and reduced costs.Clinical Trial Registration: NCT05059236.