Evolocumab in Metastatic Castration-Resistant Prostate Cancer

Elevated lipids called ceramides are associated with poorer outcomes in men with prostate cancer. Statins, a class of drug that reduces lipid levels, have been shown to be somewhat helpful in reversing this poor prognostic lipid signature, however only in a subset of men with metastatic castration-resistant prostate cancer (mCRPC) (i.e. those that are resistant to anti-androgen treatment). Therefore, other more potent or targeted lipid lowering drugs such as the anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody (PCSK9) inhibitor evolocumab may be required. This study aims to assess whether evolocumab reduces ceramide levels in men with mCRPC commencing chemotherapy or androgen receptor signaling inhibitors (ARSI) therapy. Who is it for? You may be eligible for this study if you are aged 18 years or over, have been diagnosed with mCRPC, and are planned to commence chemotherapy (docetaxel or cabazitaxel) or ARSI therapy (abiraterone or enzalutamide). Study details All participants will receive 420mg of evolocumab administered subcutaneously (i.e. injected under the skin) every 4 weeks for 12 weeks, commencing on day 1 of the first dose of chemotherapy or ARSI therapy. After each dose of evolocumab, participants will be monitored for any side effects. Blood samples will also be taken at baseline and after 12 weeks of treatment to assess for changes in the circulating lipid profile (i.e. ceramide levels) and prostate-specific antigen (PSA) levels. It is hoped that this study may show that evolocumab reduces ceramide levels associated with poor prognosis in men with mCRPC.