Is Lutetium-177 (Lu 177) effective for treating prostate cancer after Docetaxel is no longer effective?

From the Guidelines

Lutetium-177 (Lu-177) is an effective treatment for prostate cancer after docetaxel is no longer effective, as it has been shown to improve overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after docetaxel chemotherapy. The treatment, specifically Lu-177-PSMA-617 (Pluvicto), targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering targeted radiation to tumors while limiting damage to surrounding healthy tissue 1. The standard regimen involves six cycles administered intravenously every 6 weeks. Clinical trials have demonstrated that Lu-177-PSMA therapy can improve overall survival and progression-free survival in men who have exhausted other treatment options including docetaxel 1.

Key Points

• Patients must have PSMA-positive tumors confirmed by PET imaging to be eligible for this treatment.
• Common side effects include dry mouth, nausea, fatigue, and potential bone marrow suppression leading to anemia or reduced blood counts.
• Lu-177 works by binding to PSMA receptors that are overexpressed on prostate cancer cells, delivering beta radiation directly to tumor sites, which damages cancer cell DNA and leads to cell death while minimizing exposure to healthy tissues.
• The NCCN Prostate Cancer Panel recommends Lu-177-PSMA-617 as a category 1, useful in certain circumstances, treatment option for patients with at least one PSMA-positive lesion and/or metastatic disease that is predominately PSMA-positive and with no dominant PSMA-negative metastatic lesions who have been treated previously with androgen receptor-directed therapy and a taxane-based chemotherapy 1.

Treatment Considerations

• The optimal sequence of therapies remains undefined, but some data suggest that giving the alternate novel hormone therapy may not be the optimal strategy considering the availability of other treatment options, including chemotherapy 1.
• The TheraP trial compared PSA response after Lu-177-PSMA-617 vs cabazitaxel in patients with PSMA-positive mCRPC who previously received docetaxel, and found that Lu-177-PSMA-617 had a higher PSA response rate and fewer grade 3-4 adverse events 1.

From the Research

Effectiveness of Lutetium-177 (Lu 177) after Docetaxel

• The effectiveness of Lu 177 in treating prostate cancer after Docetaxel is no longer effective has been studied in several trials 2, 3, 4, 5, 6.
• A phase 2 non-inferiority trial compared the efficacy and safety of 177Lu-PSMA-617 and docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer patients, and found that 177Lu-PSMA-617 was non-inferior to docetaxel in terms of prostate-specific antigen response rate (PSA-RR) 2.
• Another study reported that 44.9% of patients who received LuPSMA therapy experienced a decline in PSA level of 50% or more, with low or minimal toxicity 3.
• A single-arm, single-centre, phase 2 study found that 57% of patients achieved a PSA decline of 50% or more after receiving [177Lu]-PSMA-617 radionuclide treatment 4.
• A systematic review of the current literature on Lutetium-177 PSMA for the treatment of metastatic castrate resistant prostate cancer found that 177Lu-PSMA-617 has been approved for treatment of mCRPC based on positive phase III studies, and is tolerable and effective 5.

Safety and Tolerability

• The safety and tolerability of Lu 177 have been evaluated in several studies, and the most common toxic effects related to [177Lu]-PSMA-617 were grade 1 dry mouth, grade 1 and 2 transient nausea, and G1-2 fatigue 4.
• Another study found that treatment-emergent grade ≥ 3 adverse events occurred less frequently with 177Lu-PSMA-617 than with docetaxel 2.
• The literature suggests that 177Lu-PSMA radioligand therapy is well tolerated and effective, and is being implemented in a growing number of centers worldwide 6.

Clinical Implications

• The findings of these studies suggest that Lu 177 may be an effective treatment option for patients with prostate cancer who have progressed after Docetaxel 2, 3, 4, 5.
• The use of Lu 177 in earlier lines of therapy and potentially in combination with other prostate cancer treatments may be considered in the future 5.