Preliminary efficacy, tolerability, and safety analysis of Darolutamide for metastatic castration‑resistant prostate cancer: a single-center, open-label study.

Abstract

Darolutamide is a structurally unique second-generation androgen receptor antagonist that has been approved for indications in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). The aim is to assess the efficacy and safety of Darolutamide for mCRPC. In this single-center, open-label, phase 1 study, patients with previously untreated mCRPC were enrolled and received androgen deprivation therapy (ADT, goserelin acetate 3.6 mg every 28 days) and docetaxel (75 mg per square meter of body surface area every 21 days) with Denosumab (120 mg every 28 days) for bone metastases, Darolutamide (300 mg orally twice daily) in the experimental group, and the control group received the corresponding of placebo. Serum PSA changes were detected and recorded, and imaging changes and adverse events (AEs) were evaluated. The primary endpoints were the safety, tolerability, and antitumor efficacy and the second endpoint was the radiographic progression-free survival (rPFS). 37 patients with mCRPC were enrolled. The median time to PSA50 in the Darolutamide group was 1.5 months (95%CI 0.2619- 0.9545), significantly lower than that in the placebo group (3.0 months [95%CI 1.048- 3.818], p= 0.0259); The median time to PSA90 in the experimental group was 4 months (95%CI 0.3094- 1.437), 2 months shorter than that in the placebo group (6.0 months [95%CI 0.6961- 3.232]).With the median follow-up of 6 months, , the median decrease in serum PSA was -81.8% (range -60.4 to -99.9%) in the Darolutamide group and -69.4% (range -50.3 to -89.6%) in the placebo group. Tumor-related pain and AEs were not increased and the median rPFS was not reach. The combination of Darolutamide and docetaxel was well tolerated with more clinically beneficial than docetaxel alone in previously untreated mCRPC. Darolutamide rapidly reduced PSA levels and prolonged rPFS, and did not increase the incidence of AEs.