Evaluating the effectiveness and safety of ipatasertib plus abiraterone and prednisolone for the treatment of patients with metastatic castration-resistant prostate cancer.

This study evaluated the effectiveness and safety outcomes of ipatasertib (GDC-0068) in combination with abiraterone acetate (Zytiga) plus prednisone (Deltasone) (AAP) for the treatment of patients with previously untreated metastatic castration-resistant prostate cancer (mCRPC). The data showed that ipatasertib plus AAP significantly improved survival without cancer worsening among patients with mCRPC and PTEN loss.

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. PTEN is a protein that controls cell processes like survival, replication, and movement within the body. It is used as a marker of PC where the loss of PTEN can suggest a poor prognosis (the likely outcome) following treatment. PTEN is functionally lost in 50% of men with mCRPC.

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. Ipatasertib is a treatment that blocks a specific protein involved in cancer cell growth, movement, and death. The combination of AA and P (AAP) is approved for the treatment of mCRPC. However, whether the addition of ipatasertib to AAP in patients with mCRPC improves the outcomes of these patients is still under investigation. 

This study involved 1101 men with previously untreated mCRPC. 521 patients had tumors with PTEN loss and were considered to have poorer outcomes. Patients were randomly assigned into 2 groups. Group 1 included 547 patients (260 with PTEN loss) who received ipatasertib plus AAP. Group 2 included 554 patients (261 with PTEN loss) who received a placebo plus AAP. The average follow-up time was 19 months.

In patients with PTEN loss, the average survival without cancer worsening was 18.5 months for group 1 compared to 16.5 months in group 2. Patients in group 1 were 23% more likely to survive without cancer worsening than patients in group 2. This difference was considered significant.

In the overall population, the average survival without cancer worsening was 19.2 months for group 1 compared to 16.6 months in group 2. Patients in group 1 were 16% more likely to survive without progression or cancer worsening than patients in group 2. This difference was not considered significant.

70% of patients in group 1 experienced severe side effects compared to 39% of patients in group 2. The most common side effects were rash, diarrhea, an increase in blood sugar levels in the blood, and an increase in liver enzymes (indicating liver damage).

This study concluded that ipatasertib plus AAP significantly improved survival without progression or cancer worsening among patients with mCRPC and PTEN loss.

This study was funded by Roche, the manufacturers of ipatasertib. Most of the tumor samples tested for PTEN loss were not fresh. This might have influenced the results.