Analyzing the effectiveness and safety of Lutetium-177–labeled PSMA–targeted therapy in patients with metastatic castration-resistant prostate cancer.

This study reviewed the effectiveness and safety of lutetium-177 [177Lu]-prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The data showed that PRLT was associated with good outcomes and manageable side effects.

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 177Lu-PSMA. 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. 177Lu-PSMA 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.

The two most common 177Lu-PSMA-targeted ligands are 177Lu-PSMA-617 and 177Lu-PSMA-I&T (imaging and treatment). However, studies reviewing the effectiveness and toxicity of different PRLT for the treatment of patients with mCRPC are missing.

This study analyzed 24 studies involving 1192 patients with mCRPC. 927 patients were treated with 177Lu-PSMA-617, 133 patients were treated with 177Lu-PSMA-I&T, and 132 with a combination of the 2. Effectiveness was measured through reductions in prostate-specific antigen (PSA; protein made by the prostate gland) levels of 50% or more compared to before treatment. 

44% of men who received 177Lu-PSMA-617 showed a PSA reduction of 50% or more compared to 36% of men who received 177Lu-PSMA-I&T. Overall, 46% of men who were treated with more than one cycle of PRLT with either 177Lu-PSMA-617 or 177Lu-PSMA-I&T showed a PSA reduction of 50% or more.

Patients who had a more than 50% reduction in PSA levels were 47% less likely to have disease progression. The estimated proportion of patients with severe side effects was less than 10%. Most side effects were mild and moderate and included nausea, tiredness, diarrhea, and elevated liver enzymes.

This study concluded that 177Lu-PRLT was effective and had a low rate of side effects in patients with mCRPC.

None of the studies analyzed in this review were randomized. The differences in the dose of the radioligand provided and previous therapies might influence some conclusions.