Evaluating the long-term effectiveness and safety of adding abiraterone acetate and prednisolone with or without enzalutamide in patients with metastatic prostate cancer starting androgen-deprivation therapy.

The study evaluated the long-term effectiveness and safety outcomes of adding abiraterone acetate (AA; Zytiga) and prednisolone (P; Deltasone) with or without enzalutamide (Xtandi) in patients with metastatic prostate cancer (PC) starting androgen-deprivation therapy (ADT). The data showed that enzalutamide and AA+P should not be combined for patients with metastatic PC starting long-term ADT. Clinically important improvements in survival from the addition of AA+P to ADT can be maintained for longer than 7 years.

Patients with metastatic PC have prostate cancer that has spread beyond the prostate gland. Generally, these patients are treated with hormone 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.

Abiraterone acetate (AA) is a medication that stops the production of male sex hormones. Therefore, it slows down prostate cancer growth. Prednisone (P) is a corticosteroid usually given in combination with AA to treat patients when they are no longer sensitive to ADT (castrate-resistant). Enzalutamide is an anti-androgen medication. It blocks testosterone from reaching PC cells.

The addition of AAP to ADT is known to improve the outcomes of patients with metastatic (spread) PC. However, the long-term effectiveness and safety outcomes of adding AAP with or without enzalutamide in men with metastatic PC starting ADT are still unknown.

This study analyzed other 2 studies and involved a total of 1919 men with metastatic PC. For the first study, 1003 patients were randomly assigned to receive either AAP with ADT (501) or ADT alone (502). For the second study, 916 patients were randomly assigned to receive either AAP plus enzalutamide with ADT (462) or ADT alone (454). AA was given at 1000 mg/day, prednisolone at 5 mg/day, and enzalutamide at 160 mg/day. The average follow-up time was 96 months for the first study and 72 months for the second study.

In the first study, the average overall survival was 76.6 months in the AAP plus ADT group versus 45.7 months in the ADT alone group. Patients who received AAP plus ADT were 38% more likely to have a better overall survival than patients who received ADT.

In the second study, the average overall survival was 73.1 months in the enzalutamide plus AAP with ADT group versus 51.8 months in the ADT alone group. Patients who received enzalutamide plus AAP with ADT group were 35% more likely to have a better overall survival than patients who received ADT.

In the first study, the serious side effects were higher in the AAP plus ADT group (54%) than in the ADT alone group (38%).

In the second study, the serious side effects were higher in the enzalutamide plus AAP with ADT group (68%) than in the ADT alone group (45%). The most common side effects were tiredness, high blood pressure, and liver dysfunction. 

This study concluded that while adding enzalutamide to AAP and ADT in patients with metastatic PC is more effective than ADT alone, the addition to enzalutamide is not better than APP and ADT combination. It also concluded that clinically important improvements in survival from the addition of AAP to ADT are maintained for longer than 7 years.

The study was funded by Janssen, the manufacturers of AA, and by Astellas, the manufacturers of enzalutamide. The patients knew which treatment they were getting which may affect the results.