Comparative Assessment of Efficacies Between 2Alternative Therapeutic Sequences With NovelAndrogen Receptor-Axis-Targeted Agentsin Patients With Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer.

Abstract

The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor-axis-targeted (ARAT) agents in patients with docetaxel-naïve metastatic castration-resistant prostate cancer (mCRPC). This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively. Of these patients, 49 and 59 received ARAT therapy with the AA-to-Enz sequence (AA-to-Enz group) and with the reverse sequence (Enz-to-AA group), respectively. No significant differences in the baseline characteristics were noted between the 2 groups. In the overall patient population, the PSA response rate to the second-line ARAT agent (21.3%) was significantly lower than that of the first-line ARAT agent (58.3%). The combined PSA PFS in the AA-to-Enz group (median, 18.4 months) wassignificantly superior to that of the Enz-to-AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (ie, AA-to-Enz vs. Enz-to-AA group) in addition to performance status as an independentpredictor of combined PSA PFS in these patients. However, there was no significant difference in overall survival (OS) between the 2 groups. Although cross-resistance between ARAT agents is a common phenomenon in docetaxel-naïve patients with mCRPC, different efficacies were observed favoring the AA-to-Enz rather than Enz-to-AA sequence in this series with respect to combined PSA PFS but not OS.