Rational Second-Generation Antiandrogen Use in Prostate Cancer

Jacob J. Orme, Lance C. Pagliaro, J. Fernando Quevedo, Sean S. Park, Brian A. Costello

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)110-124
Number of pages15
Issue number2
StatePublished - Feb 2022


  • abiraterone
  • apalutamide
  • castration resistance
  • darolutamide
  • enzalutamide

ASJC Scopus subject areas

  • General Medicine


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