A PSMA ligand linked to radioactive lutetium-177 (Lu-177) is a promising therapeutic agent to treat patients with metastatic castration-resistant prostate cancer (mCRPC), according to a recent retrospective study.
“German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients,” published in The Journal of Nuclear Medicine, reveals that nearly half of mCRPC patients responded to therapy with Lu-177-PSMA-617, which largely exceeds the response rates for other third-line treatments.
Prostate-specific membrane antigen (PSMA) is found at high levels in prostate cancers — more so in castration-resistant disease and in metastasis. Numerous studies have focused on using agents that target the prostate cancer-specific protein to deliver radioactive compounds into the cancer cells. (Castrate-resistant prostate cancer (CRPC) is cancer that no longer responds to hormone (ADT) therapy and is continuing to progress.)
“Previous studies with small number of patients have indicated the high potential of this new therapeutic option,” Kambiz Rahbar, MD, University Hospital Muenster, said in a press release. “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.”
The study examined the outcomes of the 145 mCRPC patients treated with Lu-177-PSMA-617 in one of 12 therapy centers across Germany. A total of 248 therapy cycles were administered during the study, which ran from February 2014 to July 2015, and each patient received one to four therapy cycles.
Prostate-specific antigen (PSA) levels were measured before radioligand therapy and at two- to four-week intervals. The therapy’s efficacy was defined by a decline in PSA levels of 50% or more from baseline.
Overall, 45% of the patients had a positive response, and 40% responded after a single cycle.
Side effects included red blood cell toxicity, anemia, dry mouth, and reduction in platelet levels or the number of white blood cells. Researchers said the effects were all manageable.
Nineteen patients died during the observation period.
The findings suggest Lu-177-PSMA-617 radioligand therapy is safe and more effective than current therapies used for mCRPC patients, the researchers wrote. Phase 2 and 3 studies are warranted to understand whether the treatment can help improve improve survival rates, they said.
“This therapeutic will provide an additional therapy option for end-stage metastasized, heavily pretreated prostate cancer patients,” Rahbar said. “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.”
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