Which hormonal therapy should be first in patients with castration-resistant metastatic prostate cancer?

This study analyzed and evaluated which hormonal therapy should be given first, abiraterone acetate (Zytiga) plus prednisone (Deltasone) (AAP) or enzalutamide (Xtandi; ENZ) in patients with metastatic castration-resistant prostate cancer (mCRPC). The data showed that AAP followed by ENZ is more effective in delaying disease progression compared to ENZ followed by AAP.

Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive form of prostate cancer that has spread beyond the prostate gland and is no longer responsive to hormonal therapy such as androgen deprivation therapy (ADT). ADT reduces the production of androgens (male sex hormones such as testosterone). Reducing these androgens prevents cancer cell growth. Men with mCRPC usually have high levels of prostate-specific antigen (PSA). PSA is a protein made by the cells of the prostate gland. It is used as a marker of cancer progression when it rises after treatment.

Abiraterone acetate (AA) is a medication that blocks the effect of male sex hormones. Therefore, it slows down prostate cancer growth. Prednisone (P) is a corticosteroid usually given in combination with AA to treat mCRPC. Enzalutamide (ENZ) is an anti-androgen medication. It blocks testosterone from reaching PC cells. It is also used for the treatment of mCRPC.

Both AAP and ENZ have shown to improve survival in patients with mCRPC who were previously treated with docetaxel (Taxotere). However, which sequence of treatment (AAP followed by ENZ or ENZ followed by AAP) provides the most clinical benefit is not known.

This study reviewed 17 articles studying the impact of AAP and ENZ treatments on patients with mCRPC. 2 studies directly compared both treatment sequences AAP followed by ENZ and ENZ followed by AAP.

AAP followed by ENZ showed a significantly longer survival without progression of PSA compared to ENZ followed by AAP treatment sequence. AAP followed by ENZ was associated with a 46% lower risk of PSA rising compared to ENZ followed by AAP. 

In patients previously treated with docetaxel, PSA response rates higher with AAP followed by ENZ than with ENZ followed by AAP. 

This study concluded that AAP followed by ENZ is more effective in delaying disease progression compared to ENZ followed by AAP for the treatment of patients with mCRPC.

The studies included had different patient populations and different methodologies. Further direct comparisons are needed.