Rational Second-Generation Antiandrogen Use in Prostate Cancer

In this report, we collected at all available evidence for the use of second-generation antiandrogens in prostate cancer. We outlined a rational strategy for the use of these and related treatments in metastatic castration-sensitive and both nonmetastatic and metastatic castration-resistant disease. The second-generation antiandrogens have achieved an ever-growing list of approvals and indications in subsets of prostate cancer. Here, we provide an overview of second-generation antiandrogen trials and FDA approvals and outline a rational sequencing approach for the use of these agents as they relate to chemotherapy and other available treatment modalities in advanced prostate cancer. All published phase II-III randomized controlled trials reporting outcomes with the use of second-generation antiandrogens in prostate cancer are included as well as all published trials and retrospective studies of second-generation antiandrogen sequencing and/or combinations. Complete tabular and graphical representation of all available evidence is provided regarding the use and sequencing of second-generation antiandrogens in prostate cancer. In metastatic castration-resistant prostate cancer, evidence suggests prioritization of abiraterone before chemotherapy, chemotherapy after second-generation antiandrogen failure, and postchemotherapy enzalutamide in select patients to maximize agent efficacy and tolerability. We conclude that a rational, optimized sequencing of second-generation antiandrogens with other treatment options is feasible with present data.

Automated summary

This report provides a comprehensive overview of the evidence and rational sequencing strategies for the use of second-generation antiandrogens in prostate cancer treatment. It highlights the growing list of approvals and indications for these drugs and suggests a prioritization sequence for their use in different stages of the disease. The report concludes that an optimized sequencing of second-generation antiandrogens with other treatment options is feasible based on current data.