Treatment sequencing of abiraterone acetate plus prednisone and enzalutamide in patients with metastatic castration-resistant prostate cancer

First-line therapy for advanced prostate cancer typically involves hormonal therapy using medical or surgical castration. Unfortunately, most advanced prostate cancers acquire resistance to the initial hormonal therapy and progress to metastatic castration-resistant prostate cancer (mCRPC). In recent years, novel hormonal therapies targeting the androgen-receptor axis have become available for mCRPC, including the CYP17 inhibitor, abiraterone acetate, and the androgen receptor antagonist, enzalutamide. Currently, there is no expert consensus on the treatment sequencing of abiraterone acetate plus prednisone or enzalutamide in patients with mCRPC, though historical clinical trial evidence suggests that the sequencing of hormonal therapies may impact clinical outcomes in these patients. More recently, the balance of evidence from five retrospective and two prospective clinical trials in patients with mCRPC suggests that sequencing abiraterone acetate plus prednisone before enzalutamide as first-line therapy for mCRPC may provide greater clinical efficacy (as assessed by prostate-specific antigen and progression-free survival outcomes) than sequencing enzalutamide before abiraterone acetate plus prednisone, as well as potentially providing benefits on patient quality of life. However, no significant differences in overall survival were reported. Further evidence from appropriately-designed prospective trials is required to confirm these findings.