Evaluating the effectiveness and safety of 225Ac-PSMA-617 after treatment with androgen deprivation therapy in patients with metastatic castration-resistant prostate cancer.

This study evaluated the effectiveness and safety of actinium-225 [²²⁵Ac]-PSMA-617 (225AcPSMA) after treatment with androgen deprivation therapy (ADT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The data showed that 225AcPSMA treatment showed a higher response with manageable effects in 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 after treatment with ADT in patients with mCRPC.

This study involved 53 patients with mCRPC who were previously treated with ADT. All patients received 225AcPSMA with an average number of 3 cycles. The average follow-up time was 55 months. 

96% of the patients who received 225AcPSMA showed a prostate-specific antigen (PSA; protein made by the prostate gland) reduction and 91% of the patients who received 225AcPSMA showed a PSA reduction of 50% or more.

The average overall survival was not reached (exceeded the average follow-up time) in patients with a PSA reduction of more than 50%. The average overall survival was 9 months in patients with a PSA reduction of less than 50%.

The average survival without cancer worsening was 22 months in patients with a PSA reduction of more than 50%. The average survival without cancer worsening was 4 months in patients with a PSA reduction of less than 50%.

PSA reduction of more than 50% was significantly associated with longer overall survival and a longer survival without cancer worsening.

The most common side effect was dry mouth in 81% of the patients.

This study concluded that [²²⁵Ac]PSMA-617 treatment showed a higher PSA response with manageable effects in men with mCRPC after treatment with ADT.

This study looked back in time at medical records. This study did not have a control group. Future studies are required to compare 225AcPSMA with the standard of care treatment options like enzalutamide (Xtandi) and abiraterone acetate (Zytiga).