Enzalutamide versus abiraterone acetate for the treatment of men with metastatic castration-resistant prostate cancer.

Published

Journal Article (Review)

INTRODUCTION: Over the past decade, treatment options for men with metastatic castration-resistant prostate cancer (CRPC) have expanded with the addition of abiraterone acetate (AA), enzalutamide, sipuleucel-T, radium-223, docetaxel and cabazitaxel. The optimal sequencing of therapies in the context of efficacy and known cross-resistance remains uncertain. AREAS COVERED: We review the development of enzalutamide (MDV3100, Xtandi), a novel second-generation androgen receptor (AR), and AA (Zytiga), a selective, irreversible inhibitor of cytochrome P17. In addition to discussing the clinical evidence, we also address evolving evidence of mechanisms of resistance and clinical cross-resistance during sequential therapy with these agents. EXPERT OPINION: AA and enzalutamide have both demonstrated tolerability and clinical benefit for multiple outcomes in patients with CRPC, in both post-chemotherapy and pre-chemotherapy settings. Both agents target the androgen-signaling pathway and have similar efficacy; however, they differ in prednisone use and their toxicity profiles, impacting the decision of upfront therapy. Mechanisms of resistance emerging after treatment include both alterations in AR signaling as well as mechanisms that bypass the AR. Retrospective analyses have demonstrated evidence that sequential treatment with these agents results in limited clinical benefit, supporting mechanisms of cross-resistance. Trials are ongoing to determine optimal timing, sequence and combination of these agents.

Full Text

Duke Authors

Cited Authors

  • Zhang, T; Zhu, J; George, DJ; Armstrong, AJ

Published Date

  • March 2015

Published In

Volume / Issue

  • 16 / 4

Start / End Page

  • 473 - 485

PubMed ID

  • 25534660

Pubmed Central ID

  • 25534660

Electronic International Standard Serial Number (EISSN)

  • 1744-7666

Digital Object Identifier (DOI)

  • 10.1517/14656566.2015.995090

Language

  • eng

Conference Location

  • England