Enzalutamide for the treatment of nonmetastatic castration-resistant prostate cancer

ABSTRACT

Introduction

Enzalutamide is the first characterized second-generation nonsteroidal androgen receptor inhibitor (ARi). Its efficacy has been established in several clinical trials evaluating its role in different settings of prostate cancer. Recently, enzalutamide has been approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC).

Areas covered

In this paper, the authors describe the chemical structure and pharmacologic characteristics of enzalutamide, providing a summary of clinical trials evaluating its efficacy and safety in prostate cancer patients.

Expert opinion

Enzalutamide adds to the growing arsenal of ARi used in nmCRPC. An improvement in metastasis-free survival was observed with the use of these new treatment options; recently released preliminary data report also an OS benefit. These novel agents are generally well tolerated, but their safety profiles differ slightly. Since head-to-head comparisons between ARi in nmCRPC are lacking, the adverse events profile, as well as drug availability, costs, and considerations on treatment-sequencing, would most likely influence the selection of the individual agent in this setting. Further research is needed to improve treatment selection and clarify many unsolved issues.

Abbreviations ARi: nonsteroidal androgen receptor inhibitor; nmCRPC: nonmetastatic castration resistant prostate cancer; ADT: androgen deprivation therapy; OS: overall survival; PSA: prostate specific antigen; FDA: Food and Drug Administration; AR: Androgen Receptor; MFS: metastasis free survival; PSA-DT: PSA doubling time; HR: hazard ratio; CI: confidence interval; AEs: adverse events; mCRPC: metastatic castration resistant prostate cancer; mHSPC: metastatic hormone-sensitive prostate cancer; rPFS: radiographic progression-free survival; OR: odds ratio.

KEYWORDS:

• Androgen receptor antagonist
• enzalutamide
• nonmetastatic castration-resistant prostate cancer
• nonsteroidal androgen receptor inhibitors
• prostate cancer

Declaration of interest

U Di Giorgi discloses serving as a consultant/advisory board member for Astellas, Bayer, Bristol-Myers Squibb, Ipsen, Janssen, Merck & Co, Pfizer and Sanofi, and has received travel support from Bristol-Myers Squibb, Ipsen, Janssen and Pfizer. He has also received research funding from AstraZeneca, Roche and Sanofi (via their Institution). Meanwhile, A Altavilla has received speaker’s honoraria from Janssen-Cilag while V Conteduca has received speaker’s honoraria or travel support from Astellas, Janssen-Cilag, and Sanofi. V Conteduca has also received consultancy fees from Bayer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee declares funding/honoraria/advisory board and/or speaker fees from Astellas, Amgen, Janssen, Ipsen, Sanofi and Pfizer. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript has not been funded.