Efficacy, Prognostic Factors, and Safety Profile of Enzalutamide for Non-metastatic and Metastatic Castration-Resistant Prostate Cancer: A Retrospective Single-Center Analysis in Japan

Background: Enzalutamide is a novel, non-steroidal anti-androgen that has demonstrated excellent anti-tumor activity for both non-metastatic and metastatic castration-resistant prostate cancer (nmCRPC and mCRPC) patients, and that is being rapidly introduced into clinical practice in Japan.

Objective: We retrospectively investigated the treatment efficacy, safety profile, and prognostic factors of enzalutamide over a relatively long observation period in Japanese patients with nmCRPC and mCRPC.

Patients and methods: The medical records of 184 consecutive Japanese patients with nmCRPC and mCRPC who started enzalutamide treatment in our institution between January 2012 and April 2018 were reviewed. Efficacy and safety profiles were assessed and statistically analyzed.

Results: Among these 184 patients, 44 (23.9%) nmCRPC patients, 89 (48.4%) docetaxel-naïve mCRPC patients, and 51 docetaxel-pretreated (27.7%) mCRPC patients underwent enzalutamide therapy. The median prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS) periods for nmCRPC patients were 39.2 months and not reached; those for docetaxel-naïve mCRPC patients were 16.5 months and 59.8 months; and those for docetaxel-pretreated mCRPC patients were 7.0 months and 30.4 months, respectively. Multivariate analysis identified performance status ≥ 2, PSA > 8.89 ng/mL (median value), hemoglobin < lower limit of normal range, neutrophil to lymphocyte ratio > 3.0, and 4-week PSA decline < 50% as the predictive factors for shorter OS. Our respective prognostic models using these factors successfully demonstrated distinctly separated survival curves (p < 0.001). In addition, among these patients, 30 (16.3%) experienced adverse events and 16 (8.7%) experienced adverse events resulting in the discontinuation of therapy. Fatigue (14%) and appetite loss (7%) were the most common such events.

Conclusions: Both the survival period and risk factors were extracted from a relatively long-term observation period. Since enzalutamide was approved for administration to patients with castration-sensitive prostate cancer earlier this year (2020), we believe that the data presented here will be useful for both physicians and patients in clinical practice.