Prognostic Parameters for Response to Enzalutamide After Docetaxel and Abiraterone Treatment in Metastatic Castration-Resistant Prostate Cancer Patients:a Possible Time Relation

Metastatic castration-resistant prostate cancer (mCRPC) is a prevalent and incurable disease, associated with high morbidity and mortality [1]. In recentyears multiple drugs have become available that showed an increased quality of life and overall survival (OS) of mCRPC patients. Abiraterone acetate in combination with prednisone (AA) and Enzalutamide (Enz) both target the androgen receptor and both have proven efficacy in patients with mCRPC [2–5]. Enz inhibits Androgen-Receptor (AR) signaling through inhibition of androgen binding to the AR, reducing the efficiency of the AR complex nuclear translocation, preventing the AR complex from binding to response elements in the DNA and recruitment of its coactivators [3], while AA inhibitsthe synthesis of testosterone [6]. Several retrospective studies evaluated the efficacy of Enz in mCRPC patients previously treated with Docetaxel (Doc) andAA. The rate of PSA responses (50% PSA decline) varied between 12.8% and 39.1% [7–13], OS and Progression Free Survival (PFS) varied between4.8–8.5 months [7,9,11] and between 2.9–4.0 months [7–9,12], respectively. The reported PSA response rates, OS and PFS of Enz after Doc and AA treatment were all lower than the 54%, 18.4 months and 8.3 months, respectively, reported in mCRPC patients previously treated with Doc only [3]. These resultssuggest a significant clinical cross-resistance, however, a proportion of patients treated with Enz previously treated with Doc and AA did have a PSAresponse. Here we report the characteristics of these patients. This information might be of value for optimal sequencing of treatment options for mCRPC patients