Radiolabeled Ligands Targeting PSMA May Benefit Men With Advanced Prostate Cancer

A new German multicenter study is suggesting that lutetium-177 (Lu-177)-labeled PSMA-617 may be a promising new therapeutic agent for radioligand therapy (RLT) in men with metastatic castration-resistant prostate cancer (mCRPC). The study, which is published in the January 2017 issue of The Journal of Nuclear Medicine, demonstrated that Lu-177-PSMA-617 radioligand therapy is safe and more effective than other third-line systemic therapies for men with mCRPC.

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer and to an even greater degree with castration-resistant disease. The development of new tracers for PSMA-targeted radionuclide therapies are now under investigation and show promise. It is theorized that targeted radionuclide therapy may have a significant advantage because it can spare normal tissue while giving a high radiation dose to the tumor. Therapy Lu177 is a medium-energy β-emitter with a maximum energy of 0.5 MeV and a maximal tissue penetration of 2 mm. Its half-life is 6.7 days. 

“Previous studies with small number of patients have indicated the high potential of this new therapeutic option,” said study author Kambiz Rahbar, MD, who is with University Hospital Muenster in Germany. “This study of a large number of patients at multiple healthcare facilities, however, confirms the efficacy and safety of Lu-177-PSMA-617 radioligand therapy.”

At 12 therapy centers across Germany, 145 patients with mCRPC were treated with Lu-177-PSMA-617 between February 2014 and July 2015. The median age of the patients 73 years (range: 43-88 years old) and they were all treated with one to 4 therapy cycles. Investigators examined data on 248 therapy cycles performed in 145 patients. Efficacy was defined by a prostate-specific antigen (PSA) decline of 50% or more from baseline to at least 2 weeks after start of RLT. 

The investigators had data for biochemical response in 99 patients. They had data for physician-reported data in 145 patients and laboratory-based toxicity data in 121 patients.  The median follow-up was 16 weeks (range: 2 to 30 weeks). During the observation time, 19 patients died. Overall, 45% of patients had a positive response following all therapy cycles, with 40% responding after a single cycle. The study demonstrated that elevated alkaline phosphatase and the presence of visceral metastases were negative predictors. The total numbers of therapy cycles were positive predictors of biochemical response.

Some adverse side effects were noted, but manageable. Hematotoxicity occurred in 18 patients (10% experienced anemia; 4% thrombocytopenia and 3% leukopenia). Xerostomia was experienced by 8%.

Dr. Rahbar said this therapy may be a new option for end-stage metastasized, heavily pretreated prostate cancer patients.  However, he and colleagues caution that future phase II and III studies are warranted to clarify the survival benefit of this new therapy.  Dr. Rahbar said since this approach has demonstrated remarkably high response rates and low toxicity it may be that this therapy could also be highly beneficial at earlier stages of disease.