Advances with androgen deprivation therapy for prostate cancer

ABSTRACT

Introduction

Androgen deprivation therapy (ADT) has been a treatment of choice for prostate cancer in almost all phases, particularly in the locally advanced, metastatic setting in both hormone-sensitive and castration-resistant diseaseand in those who are unfit for any local therapy. Different ways of administering ADT comes in the form of surgical or chemical castration with the use of gonadotropin-releasing hormone (GnRH-agonists) being the foremost way of delivering ADT.

Areas covered

This review encompasses ADT history, use of leuprolide, degarelix, and relugolix, with contextual use of ADT in combination with androgen-signaling inhibitors and potential mechanisms of resistance. Novel approaches with regard to hormone therapy are also discussed.

Expert opinion

The use of GnRH-agonists and GnRH-antagonists yields efficacy that is likely equivalent in resulting in testosterone suppression. While the side-effect profile with ADT are generally equivalent, effects on cardiovascular morbidity may be improved with the use of oral relugolix though this is noted with caution since the cardiovascular side-effects were a result of secondary subgroup analyses. The choice of ADT hinges upon cost, availability, ease of administration, and preference amongst physicians and patients alike.

KEYWORDS:

• Androgen deprivation therapy
• prostate cancer
• gonadotropin-releasing hormone agonist
• gonadotropin-releasing hormone antagonist
• relugolix

Article highlights

• Androgen deprivation therapy is the cornerstone of treatment for most phases of prostate cancer, delivered in the form of GnRH-agonists or GnRH-antagonists

• Efficacy of GnRH-agonists and antagonists are equivalent though administration and testosterone kinetics upon ADT withdrawal are different

• Relugolix is the first oral GnRH-antagonist found to be equivalent to leuprolide in efficacy but has 54% lesser cardiovascular events on subgroup data analyses

• Future studies include combination therapies with relugolix and other androgen-signaling agents

• Side-effect profiles with either GnRH-antagonists or GnRH-agonists are fairly equivalent with possible cardiovascular effects in favor of GnRH-antagonists

This box summarizes key points contained in the article.

Declaration of interest

JB Aragon-Ching currently serves on the Speakers’ Bureau of Bristol Myers Squibb and Astellas/Seattle Genetics and has served on the Advisory Board for AstraZeneca, Bayer, Immunomedics, Pfizer/EMD Serono, Merck and Co and Pfizer/Myovant. 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 reviewer has received research support and/or has consulted for and consulting for AbbVie, AstraZeneca, Ferring, Myovant/Pfizer and Tolmar. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.