Predictive factors for effectiveness from novel androgen-receptor-axis-targeted agents in patients with metastatic prostate cancer.

Abstract

33 Background: About a half of men with prostate cancer progress to metastatic castration-resistant prostate cancer (mCRPC) one year after the initiation of androgen-deprivation therapy (ADT), whereas approximately 20 % of men keep the sensitivity to ADT more than 5 years. Several novel androgen-receptor-axis-targeted agents (ARATAs) were developed for the treatment of mCRPC, and improved overall survival (OS) in patients with mCRPC; however, to which patients these ARATAs were more beneficial is yet to be determined. We conducted this study to identify factors that predict effectiveness from ARATAs for mCRPC. Methods: We previously performed a multicenter study to determine prognostic factors including bone scan index (BSI) in patients with metastatic hormone sensitive prostate cancer (n = 148) and mCRPC (n = 99), which showed that BSI was one of the significant determinants of 3-year OS (PROSTAT-BSI study). The patients with mHSPC progressed to mCRPC (n = 101). Among these mCRPC patients, 69 patients received treatments with or without ARATAs, because the patients were recruited before and after approval of ARATAs in Japan. We used the data of the 69 patients to identify predictors for effective use of ARTA. The cohort was divided into two groups according to patient factors by several thresholds, and these two cohorts were further divided into two subgroups: those who received and did not receive ARATAs (abiraterone or enzalutamide). OS was compared between these two cohort groups to evaluate contribution of each factor. Categorical values were analyzed in the same way, although no threshold setting was required. Results: Factors, in which the significant treatment effect from ARATAs was observed between subgroups in only one group (eg. age < 71.4 vs age ≥ 71.4), were age ( < 71.4 years); serum levels of C-reactive protein (≥0.16 ng/mL), alkaline phosphatase (≥548 U/L), and type 1 collagen C-terminal telopeptide ( < 6.4 ng/mL); time to PSA progression after ADT ( < 8.9 months); lowest PSA level (≥1 ng/mL) after ADT; and rate of PSA decline 3 month after ADT ( <.987). Whereas, no significant difference was observed between two groups in cohorts divided by hemoglobin level, PSA before ADT, Gleason score, and BSI. Conclusions: This study identified the predictors of the effectiveness from ARATAs. In addition, the number of bone metastases (corresponding to BSI) and Gleason score, which were considered as high-risk factors in the LATITUDE study and disease volume in the CHAARTED criteria, may not be useful for predicting the effectiveness from ARATAs.