No clear evidence of a clinical benefit of a sequential therapy regimen with abiraterone acetate and enzalutamide

Abstract

Prostate cancer is the second leading cause of cancer-related deaths in men in most western countries. New agents for metastatic castration-resistant prostate cancer (CRPC) developed in the past 3 years include abiraterone acetate (AA) and enzalutamide (ENZ), which inhibit signaling by and synthesis of androgens, respectively. Because they share the same target, potential clinical cross-resistance between AA and E is possible. In this review, we discuss the results of clinical studies in which CRPC patients were treated with AA and E either separately or in sequence after first-line treatment with docetaxel. Our review suggests that sequential administration of AA and E in either order has limited activity after docetaxel therapy. Prospective studies that further examine sequential treatments with AA and E are warranted.

Keywords::

• abiraterone acetate
• anti-androgen
• enzalutamide
• prostate cancer
• sequential therapy

Financial & competing interests disclosure

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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• In the past 3 years, several new therapies with different mechanisms of action have emerged.

• Patients who progressed during treatment with docetaxel had a modest response when subsequently treated with abiraterone acetate (AA) and enzalutamide (E) in sequence.

• Several mechanisms of intrinsic and acquired resistance between AA and E have been proposed on the basis of in vitro and in vivo studies.

• The low efficacy of sequential administration of AA and E in either order should affect the treatment decisions of chemotherapy-naïve metastatic castration-resistant prostate cancer patients.

• Clinical trials should heed the information presented in this review.