From the Guidelines
Lutetium-177 (Lu-177) is beneficial for prostate cancer patients after Docetaxel therapy fails, as it improves overall survival and quality of life in patients with metastatic castration-resistant prostate cancer. Lu-177-PSMA therapy targets prostate-specific membrane antigen (PSMA), a protein overexpressed in prostate cancer cells, delivering radiation directly to cancer cells while minimizing damage to surrounding healthy tissue.
Key Points
- The VISION trial, a phase III study, demonstrated that Lu-177-PSMA-617 improved median overall survival (OS) by 4 months (15.3 vs 11.3 months; HR, 0.62; 95% CI, 0.52–0.74; P < 0.001) and median progression-free survival (PFS) by 5.3 months (8.7 vs 3.4 months; HR, 0.40; 99.2% CI, 0.29–0.57; P < 0.001) compared to standard of care alone in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had previously received taxane-based chemotherapy and androgen receptor-directed therapy 1.
- The TheraP trial, a randomized phase II study, showed that Lu-177-PSMA-617 had a higher PSA response rate (66% vs 37%) and fewer grade 3-4 adverse events (33% vs 53%) compared to cabazitaxel in patients with PSMA-positive mCRPC who had previously received docetaxel 1.
- The ESMO clinical practice guidelines recommend considering Lu-177-PSMA-617 as a treatment option for patients with mCRPC who have previously received taxane-based chemotherapy and androgen receptor-directed therapy, based on the results of the VISION trial 1.
Treatment Details
- The typical treatment involves four to six intravenous infusions of Lu-177-PSMA-617 given approximately six weeks apart, with each session lasting a few hours.
- Patients may experience mild side effects such as fatigue, dry mouth, nausea, and temporary decreases in blood cell counts.
- Before treatment, patients typically undergo PSMA PET imaging to confirm their tumors express sufficient PSMA for the therapy to be effective.
Conclusion Not Provided as per Guidelines
Instead, the key points and treatment details are emphasized to guide clinical decision-making, prioritizing morbidity, mortality, and quality of life as the outcome.
From the Research
Lutetium-177 (LU-177) for Prostate Cancer
- LU-177, also known as Lutetium-177 PSMA, is a radioligand therapy that targets prostate-specific membrane antigen (PSMA) in prostate cancer cells.
- Studies have shown that LU-177 can be beneficial for patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after standard treatments, including docetaxel 2, 3, 4.
Efficacy of LU-177 after Docetaxel Failure
- A phase 2 trial found that 57% of patients with mCRPC who received LU-177 achieved a PSA decline of 50% or more, with a median overall survival of 19.1 months 2.
- Another study found that LU-177 improved overall survival and quality of life in patients with mCRPC who had progressed after docetaxel, with a median overall survival of 15.3 months 4.
- A randomized phase 2 trial found that LU-177 plus docetaxel improved antitumor activity in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer compared to docetaxel alone 5.
Safety and Tolerability of LU-177
- The most common adverse events associated with LU-177 were grade 1-2 dry mouth, nausea, and fatigue, with grade 3-4 thrombocytopenia occurring in 13% of patients 2.
- Another study found that the incidence of adverse events of grade 3 or above was higher with LU-177 than without, but quality of life was not adversely affected 4.
Comparison to Other Treatments
- A study found that LU-177 had similar overall survival to cabazitaxel in patients with mCRPC who had progressed after docetaxel, with a median overall survival of 19.1 months for LU-177 and 19.6 months for cabazitaxel 3.
- Another study found that LU-177 plus standard care significantly prolonged imaging-based progression-free survival and overall survival compared to standard care alone in patients with advanced PSMA-positive mCRPC 4.