Impact of Prior Use of an Androgen Receptor-Axis-Targeted (ARAT) Agent With or Without Subsequent Taxane Therapy on the Efficacy of Another ARAT Agent in Patients With Metastatic Castration-Resistant Prostate Cancer

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The assessment of efficacy in novel androgen receptor-axis-targeted (ARAT) therapies with abiraterone acetate and/or enzalutamide for docetaxel-naive metastatic castration-resistant prostate cancer showed common occurrence of cross-resistance between the ARAT agents, irrespective of the use of taxanes between these agents. Therefore, following the failure of either ARAT agent, it might be preferable to avoid the sequential administration of another ARAT agent.


The objective of this study was to investigate whether the prior use of a novel androgen receptor-axis-targeted (ARAT) agent with or without subsequent taxane therapy could affect the efficacy of another ARAT agent in patients with metastatic castration-resistant prostate cancer (mCRPC).

Patients and Methods:

This study included a total of 302 patients with mCRPC, who were treated with abiraterone acetate and/or enzalutamide. These 302 patients were classified into the following 3 groups: group A, 173 received an ARAT agent without the prior use of another ARAT agent; group B, 102 sequentially received ARAT agents without any treatment between the 2 agents; group C, 27 sequentially received ARAT agents, with taxane therapy between the 2 ARAT agents.


The response rate to the ARAT agent in group A (63.6%) was significantly higher than those to the ARAT agent introduced late-line in groups B and C (20.6% and 29.6%, respectively). In addition, prostate-specific antigen progression-free survival during the ARAT therapy in group A was significantly superior to those during the ARAT therapy conducted late-line in groups B and C. Multivariate analyses of several parameters identified the prior use of an ARAT agent, but not the administration of taxane between the ARAT therapies, as one of the independent predictors of prostate-specific antigen progression-free survival.


Cross-resistance between ARAT agents may be a common phenomenon in patients with mCRPC, irrespective of the introduction of taxane between the ARAT therapies.

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