Comparing the activity and safety of [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer

This study compared the effectiveness and safety of lutetium-177 [¹⁷⁷Lu]-PSMA-617 (177LuPSMA) versus cabazitaxel (Jevtana) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The data showed that 177LuPSMA treatment showed a higher response with fewer side 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.

mCRPC commonly requires additional therapy such as chemotherapy. Several new treatments have been introduced for mCRPC such as cabazitaxel. Cabazitaxel is a chemotherapy drug that was shown to improve survival in patients with mCRPC who were previously treated by docetaxel.

An additional treatment option is with 177LuPSMA. This is a radioactive drug that involves a small molecule called PSMA bound with a radioactive particle such as 177Lutetium. PSMA is a protein that can be found in high levels on the surface of prostate cancer. 177LuPSMA 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, studies comparing the activity and safety of 177LuPSMA versus cabazitaxel in patients with mCRPC are still under investigation.

This study involved 200 patients with mCRPC who were previously treated with docetaxel. 99 patients were randomly assigned to receive 177LuPSMA and 101 patients received cabazitaxel treatment. The average follow-up period was 18.4 months. 

66% of men who received 177LuPSMA showed a prostate-specific antigen (PSA; protein made by the prostate gland) reduction of 50% or more compared to 37% of men who received cabazitaxel.

177LuPSMA was associated with a 37% lower risk of disease progression compared to cabazitaxel. After 12 months, 19% of patients treated with 177LuPSMA were alive without disease progression compared to 3% in the cabazitaxel group.

Severe side effects occurred in 33% of men in the 177LuPSMA group compared to 53% of men in the cabazitaxel group. Side effects included fatigue, pain, and low platelet (blood cells involved in clotting) counts.

This study concluded that 177LuPSMA treatment showed a higher PSA response with fewer side effects compared with cabazitaxel in men with mCRPC.

Outcomes like overall survival and patient-reported quality of life were not measured. The follow-up period was short. This study was funded by Novartis, the manufacturer of 177LuPSMA.