Abstract: PD24-01
Sources of Funding: None

Introduction

Accumulating findings suggest that sequential treatment with androgen receptor-axis-targeted (ARAT) agents, abiraterone acetate (AA) and enzalutamide (Enz), in either order has limited efficacy for metastatic castration-resistant prostate cancer (mCRPC). Furthermore, there has been a strong trend toward the movement of novel ARAT therapies into the front-line for mCRPC treatment prior to the introduction of docetaxel within the last few years, due to the favorable tolerability of ARAT agents compared with taxanes. Considering these findings, it is still important to determine the optimal sequencing order of novel ARAT agents for mCRPC patients. The objective of this study was to compare the efficacies of sequential therapies with novel ARAT agents in patients with docetaxel-naive mCRPC.

Methods

This study included 108 consecutive mCRPC patients who sequentially received AA and 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.

Results

Of the 108 patients, 49 and 59 received ARAT therapy with the AA-to-Enz sequence (AA-to-Enz group) and that with the reverse sequence (Enz-to-AA group), respectively. No significant differences in the baseline characteristics were noted between the two groups. In the overall patient population, the PSA response rate to the second-line ARAT agent (56.5%) was significantly lower than that to the first-line ARAT agent (21.3%). The combined PSA PFS in the AA-to-Enz group (median, 18.4 months) was significantly superior to that in the Enz-to-AA group (median, 12.8 months). Furthermore, multivariate analysis identified the treatment sequence (i.e., AA-to-Enz versus Enz-to-AA group) in addition to performance status as an independent predictor of combined PSA PFS in these patients.

Conclusions

Although cross-resistance between ARAT agents is a common phenomenon in docetaxel-naive mCRPC patients, different efficacies were observed favoring the AA-to-Enz rather than Enz-to-AA sequence in this series. Thus, when ARAT agents are to be introduced sequentially, it may be advisable to provide ARAT therapy according to the AA-to-Enz sequence.

Funding

None