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. <b>Clinical Trial Registration:</b> NCT05059236 The ARASEC study is evaluating darolutamide, an androgen receptor inhibitor, plus hormonal therapy (androgen-deprivation therapy, ADT) in patients with prostate cancer that has spread beyond the prostate to other parts of the body and continues to respond to hormonal therapy. The goal of the study is to discover whether darolutamide plus ADT can delay the time until the cancer progresses and no longer responds to hormonal therapy, compared with ADT alone. To ensure that all patients participating in ARASEC receive optimal treatment, the study did not require any patients to receive ADT alone. Instead, to compare the effect of darolutamide and ADT with that of ADT alone, patients in ARASEC were matched to patients from a previous clinical study (CHAARTED) who received ADT alone. Matching was based on patient characteristics that help determine disease prognosis, including age, health status, extent of disease, and prostate-specific antigen level. This is a new way of conducting a clinical trial in patients with prostate cancer, which may pave the way for future single-arm trials to speed up enrollment (because all patients will be sure of receiving effective treatment) and therefore reduce costs of running trials.