Evaluating the effectiveness and safety of adding abiraterone acetate and prednisolone with or without enzalutamide to androgen-deprivation therapy in patients with high-risk non-metastatic prostate cancer.

The study evaluated the effectiveness and safety outcomes of adding abiraterone acetate (AA; Zytiga) and prednisolone (P; Deltasone) with or without enzalutamide (Xtandi) to androgen-deprivation therapy (ADT) in patients with high-risk non-metastatic prostate cancer (PC). The data showed that AAP added to ADT significantly improved survival without metastasis compared to ADT alone in these patients.

Patients with non-metastatic PC have prostate cancer that has not 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 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 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, studies evaluating the effectiveness and safety outcomes of adding AAP with or without enzalutamide to ADT in men with high-risk non-metastatic PC are still missing.

This study analyzed 2 studies and involved a total of 1974 men with high-risk non-metastatic PC. For the first study, 914 patients were randomly assigned to receive either AAP with ADT (459) or ADT alone (455). For the second study, 1060 patients were randomly assigned to receive either AAP plus enzalutamide with ADT (527) or ADT alone (533). AA was given at 1000 mg/day, prednisolone at 5 mg/day, and enzalutamide at 160 mg/day. The combination groups included 986 patients and the control (ADT alone) groups included 988 patients. Patients received combination therapy for up to 2 years and ADT was given for 3 years. The average follow-up time was 72 months.

After 6 years, 82% of the patients in the combination groups were alive without metastasis compared to 69% of the patients in the control groups. Patients in the combination groups were 47% more likely to survive without metastasis compared to patients in the control groups. The average survival without metastasis was significantly longer in the combination groups compared to the control groups. There was no difference in survival without metastasis when enzalutamide and AAP were given together versus AAP alone.

After 6 years, 86% of the patients in the combination groups were alive compared to 77% of the patients in the control groups. Patients in the combination groups were 40% more likely to have a better survival compared to patients in the control groups. The average overall survival was significantly longer in the combination groups compared to the control groups.

After 6 years, 93% of the patients in the combination groups were alive without PC compared to 85% of the patients in the control groups. Patients in the combination groups were 51% more likely to survive without PC compared to patients in the control groups. The average survival without PC was significantly longer in the combination groups compared to the control groups.

Biochemical failure (BCF) was also evaluated. If, after treatment, the prostate-specific antigen (PSA: a protein made by cells of the prostate gland that increases in PC) levels increased by 2 ng/ml from the lowest value it was considered as evidence of BCF. Patients in the combination groups were 61% more likely to survive without BCF compared to patients in the control groups. The average survival without BCF was significantly longer in the combination groups (exceeded the average follow-up period) compared to the control groups (86 months).

Patients in the combination groups were 56% more likely to survive without cancer worsening compared to patients in the control groups. The average survival without cancer worsening was significantly longer in the combination groups compared to the control groups.

In the first study, 37% of the patients in the combination group experienced serious side effects compared to 29% of patients in the control group. In the second study, 58% of the patients in the combination group experienced serious side effects compared to 32% of patients in the control group. The most common side effects in the combination groups in both the studies were low blood pressure and liver dysfunction.

This study concluded that AAP added to ADT significantly improved survival without metastasis compared to ADT alone for the treatment of men with high-risk non-metastatic PC. The authors recommended that AAP should be considered a new standard treatment for this population.

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.