AR-Targeted Therapies in Advanced Prostate Cancer

For High-Definition, Click

Multiple new agents have gained FDA approval in advanced prostate cancer during the past three years, particularly abiraterone acetate (Zytiga) and enzalutamide (Xtandi). These agents represent a major advance for patients with advanced prostate cancer, due to their high-level of activity and tolerable side effect profile, Raoul S. Concepcion, MD, explains.

Abiraterone was first approved following chemotherapy for men with metastatic castration-resistant prostate cancer (mCRPC) in August 2011 based findings from the COU-AA-301 study, David I. Quinn, MD, observes. In this study, the median overall survival (OS) with abiraterone was 14.8 months compared with 10.9 months with placebo. In December 2012, abiraterone was also approved along with prednisone prior to chemotherapy for men with CRPC based on results from the COU-AA-302 trial. Treatment duration with abiraterone in this trial lasted up to 18 months and demonstrated a median OS of 35.3 months compared with 30.1 months with docetaxel, Quinn explains.

The administration of prednisone is required along with abiraterone to suppress activation of a negative feedback mechanism that produces adrenocorticotropic hormone along with associated side effects. However, in his practice, Quinn slowly tapers patients off prednisone, since the combination of an androgen receptor biosynthesis inhibitor and a corticosteroid can have a negative impact on bone health.

To prevent skeletal-related events, calcium and vitamin D should be administered along with denosumab or zoledronic acid, Quinn says. Patient's liver enzymes, potassium levels, and blood pressure should be monitored closely, particularly following the first dose of abiraterone. After treatment has been administered for more than 6 months, these visits can be conducted every 3 months, Quinn suggests.

The other approved agent, enzalutamide, demonstrated an extension in survival compared with placebo in the phase III AFFIRM study that explored the drug following chemotherapy for men with mCRPC. In this investigation, the median OS was 18.4 months with enzalutamide compared with 13.6 months for placebo. The treatment was also explored prior to chemotherapy in the PREVAIL study, which showed a median OS of 32.4 months versus 30.2 months with placebo. Based on this study, the FDA is reviewing an application for enzalutamide in the prechemotherapy space, with an expected decision date set in September 2014.

There have been significant changes in the past few years, making it difficult to stay abreast with the most recent developments, David Albala, MD, believes. As a result, it is important to ensure an adequate understanding of each drug and how it can be appropriately sequenced. In addition to this, many of the recently approved agents have different mechanisms of action, E. David Crawford, MD, points out.

The multiple changes in recent years further enhances the need for multidisciplinary care, notes Steven E. Finkelstein, MD. This is a particularly important, Vahan Kassabian, MD, believes, since a patient's quality of life should always be paramount. Given the multiple advances and new imaging techniques, long-term outcomes have improved, resulting in many patients dying of other causes that are unrelated to prostate cancer and its treatment, notes Stephen J. Freedland, MD.