Prostate-specific membrane antigen (PSMA) is overexpressed in
prostate cancer and even more so with castration-resistant disease. This
makes development of new tracers for PSMA-targeted radionuclide
therapies a promising treatment approach.
Prostate cancer deaths are usually the result of metastatic castration-resistant prostate cancer (mCRPC), and the median survival for men with mCRPC has been less than two years.
A German multicenter study, initiated by the German Society of Nuclear Medicine, demonstrates that lutetium-177 (Lu-177)-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer.
At 12 therapy centers across Germany, 145 patients (median age 73 years, range 43-88) with mCRPC were treated with Lu-177-PSMA-617 between February 2014 and July 2015 with one to four therapy cycles. A total of 248 therapy cycles were performed in 145 patients.
Efficacy was defined by a prostate-specific antigen (PSA) decline of 50% or more from baseline to at least two weeks after start of RLT. Overall, 45% of patients had a positive response following all therapy cycles, while 40% responded after a single cycle.
Some adverse side effects were noted but manageable. Hematotoxicity occurred in 18 patients: 10% experienced anemia; 4%, thrombocytopenia (low platelet count); and 3%, leukopenia (low white blood cell count). Dry mouth was experienced by 8%.
The study shows that Lu-177-PSMA-617 radioligand therapy is safe and more effective than other third-line systemic therapies for mCRPC patients. Future Phase II and III studies are needed to clarify the survival benefit of this new therapy, which is not yet FDA-approved.
"This therapeutic will provide an additional therapy option for end-stage metastasized, heavily pretreated prostate cancer patients," said Rahbar. "While already demonstrating remarkably high response rates and low toxicity, in the future it may be available at earlier stages of disease with even higher response rates and lower toxicity."