An up-to-date evaluation of abiraterone for the treatment of prostate cancer

ABSTRACT

Introduction: Abiraterone acetate, an oral 17-alpha-hydroxylase inhibitor, effectively prevents the synthesis of androgens from steroid precursors. Abiraterone has become a standard of care in patients with metastatic prostate cancer due to its efficacy in both castrate-sensitive and castrate-resistant disease when given in combination with androgen deprivation therapy (ADT). Abiraterone may have a role in additional aspects of prostate cancer treatment in the future.

Areas covered: The present article focuses on the development and establishment of abiraterone among the available treatment options for prostate cancer. A literature search was performed in PubMed/Medline for prior studies and reviews of the drug. Current clinical trials were examined in the Clinicaltrials.gov database.

Expert opinion: Abiraterone has shown efficacy in castrate-resistant metastatic prostate cancer, providing an additional degree of hormonal sensitivity for tumors resistant to ADT. Impressively, abiraterone in conjunction with ADT as a first-line treatment for castrate-sensitive prostate cancer also confers a significant overall survival benefit compared to ADT alone. With minimal additional toxicity, abiraterone has established itself as a well-tolerated, convenient, and effective treatment option. Ongoing studies are expected to broaden the drug’s indications as well as its preference among other prostate cancer therapies.

KEYWORDS:

• Abiraterone
• mineralocorticoid excess syndrome
• prednisone
• prostatic neoplasms
• prostatic neoplasms
• castration-resistant
• testosterone
• 17-alpha-hydroxylase

Article Highlights

• Abiraterone acetate is an orally administered 17-alpha-hydroxylase (CYP17A1) inhibitor that prevents the conversion of steroid precursors to androgens such as testosterone.

• Through its action as an androgen synthesis inhibitor, abiraterone is FDA approvedfor the treatment of metastatic castrate-sensitive prostate cancer (mCSPC) and metastatic-castrate resistant prostate cancer (mCRPC).

• Abiraterone is generally well-tolerated with manageable adverse events including mineralocorticoid excess (i.e. hypertension, hypokalemia, fluid overload) and hepatotoxicity. Abiraterone is administered with corticosteroids to reduce incidence of mineralocorticoid excess.

• Abiraterone has certain benefits over other therapeutics in metastatic prostate cancer, such as taxanes or competitive androgen receptor antagonists. Abiraterone does not carry the risk of myelosuppression or the inconvenience of intravenous administration associated with taxanes. Abiraterone also does not appear to carry the same risk of seizures and falls associated with certain androgen receptor antagonists. Patients on abiraterone may experience superior quality of life than those on enzalutamide due to less fatigue and cognitive effects

• Given abiraterone’s specific risks of hypertension, fluid retention and hypokalemia, caution and close monitoring should be employed in patients with certain cardiac conditions. Abiraterone should be avoided in patients with severe hepatic impairment.

• Optimal sequencing of prostate cancer therapeutics remains an area of investigation. Prospective data suggests longer times to second PSA progression in patients with mCRPC treated with abiraterone followed by enzalutamide compared to those treated with enzalutamide followed by abiraterone.

• Abiraterone’s convenience, efficacy, and safety profile have established it as an integral component in the treatment of prostate cancer. Ongoing clinical trials are investigating abiraterone’s use in combination with other treatments as well as in earlier disease settings.

This box summarizes key points contained in the article.

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Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.