Darolutamide in combination with androgen deprivation therapy (ADT) and docetaxel had been proven effective to improve the overall survival of high risk metastatic castration- sensitive prostate cancer (mCSPC) and significantly reduce the risk of death by 32.5% (hazard ratio [HR] 0.68; 95% confidence interval [CI]: 0.57–0.80; P<0.001) compared with placebo plus ADT and docetaxel. From May 1st, 2024, darolutamide has been reimbursed by the National Health Insurance (NHI) for high risk mCSPC of modified definition. This study aimed to present the experiences of using darolutamide for the treatment of mCSPC in our real world clinical practice.

During the period from February 2024 to February 2025, we enrolled patients who met the NHI modified definition of high risk mCSPC and received NHI reimbursed darolutamide plus ADT and docetaxel in our hospital (VGHTPE). Adverse events (skin event, bone event, cardiac event, brain event) and serum biochemistry parameters were monitored during the whole course of darolutamide at each clinic visit. The clinical response and adverse events (AEs) were reported.

In total, 20 patients were enrolled in our study since February, 2024. Among them, 14 patients completed 6 cycles of docetaxel, and 6 patients received docetaxel treatment initiated within 6 weeks of starting darolutamide treatment. There were 4 patients undergoing docetaxel treatment currently, and 2 patients discontinued docetaxel due to adverse events. Twelve patients (85.7%) were Gleason score ≥8, 11 patients (78.6%) had four or more metastatic bone lesions and at least one at appendicular bone on bone scan, and 3 patients (21.4%) had visceral metastasis (most in lung). All of the patients (100%) met high-risk criteria. Median follow-up period was 7.5 months (4-12). Eighteen patients (90%) were still on the treatment until February 2025 with a median treatment duration of 7.5months. The PSA response rate at 3 months, defined as decline of PSA ≥ 50%, was 100%, and ultra-low PSA, defined as serum PSA < 0.02 ng/mL, was also 100%. Median time to ultra- low PSA was 6 months (3-7). The common AEs were anemia (N=8, 57.1%) and skin rash (N=2, 14.2%). Elevated liver function tests were noted in 1 patient (7.1%). There was only one AE of CTCAE grade 2 in anemia and one grade 4 in neutropenia with respiratory failure.

Our preliminary experiences showed a high PSA response rate of darolutamide in combination with ADT and docetaxel in the treatment of high-risk mCSPC. However, 2 patients suffered from treatment related AEs and discontinued the medication. Prolonged follow-up is needed for further survival outcomes.