Evaluating the effectiveness and safety of 225Ac-PSMA-617 for the treatment of patients with metastatic castration-resistant prostate cancer.

This study evaluated the effectiveness and safety of actinium-225 [²²⁵Ac]-PSMA-617 (225AcPSMA) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The data showed that 225AcPSMA was effective with manageable side effects for these patients.

Prostate cancer (PC) often grows in response to androgens (male sex hormones such as testosterone). These patients are usually treated with androgen deprivation therapy (ADT) which reduces the production of androgens. Reducing these androgens prevents cancer cell growth. 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 ADT. These patients can benefit from chemotherapies such as docetaxel (Taxotere). However, some patients have disease progression after this treatment and new therapies are needed.

An additional treatment option is with 225AcPSMA. This is a radioactive drug that involves a small molecule called PSMA bound with a radioactive particle such as 225Actinium. PSMA is a protein that can be found in high levels on the surface of prostate cancer. 225AcPSMA attaches itself to prostate cancer cells and releases radiation that kills the cancer cell. It has been shown that targeting PSMA tumor cells is effective for patients with mCRPC progressing after docetaxel therapy. However, there are few studies evaluating the effectiveness and safety of 225AcPSMA for the treatment of patients with mCRPC.

This study analyzed 6 studies and involved overall 201 patients with mCRPC. All patients received treatment with 225AcPSMA.

87% of the patients who received 225AcPSMA showed a prostate-specific antigen (PSA; protein made by the prostate gland and usually elevated in PC) reduction and 66.7% of the patients who received 225AcPSMA showed a PSA reduction of 50% or more.

The average overall survival was 12.5 months. The average survival without cancer worsening was 9.1 months. Overall, 54% of the patients responded to the treatment.

The most common serious side effects were dry mouth (3%), low red blood cell counts (7.5%), low white blood cell counts (4.5%), and low platelet cell counts (5.5%).  

This study concluded that [²²⁵Ac]PSMA-617 treatment was effective with manageable side effects for patients with mCRPC.

All studies analyzed looked back in time at medical records. All studies analyzed did not have a control group. The sample size was very small and the follow-up time was too short.