Novel radioligand therapy proven superior for metastatic prostate cancer patients

Reston, VA—A novel prostate cancer treatment—²²⁵Ac-PSMA-617 radioligand therapy—has been shown to increase the progression free survival (PFS) and overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients, according to research published by The Journal of Nuclear Medicine. Ninety-one percent of patients experienced a greater than 50 percent reduction of their initial PSA (prostate specific antigen) value after treatment with ²²⁵Ac-PSMA-617, resulting in a PFS of 22 months and an OS not yet reached at the conclusion of the study.

While the five-year survival rate of localized prostate cancer is nearly 100 percent, for mCRPC patients it is only 30 percent. Clinical studies have demonstrated the efficacy and safety of several therapies, including ¹⁷⁷Lu-PSMA in the post- androgen deprivation therapy (ADT) setting in patients with mCRPC. Additional therapies, such as ²²⁵Ac-PSMA-617, are often considered once the disease begins to progress again.

“Previous research has shown a remarkable therapeutic efficacy of ²²⁵Ac-PSMA-617 in heavily pre-treated mCRPC patients, as demonstrated by the initial work from Kratochwil et al. from Germany,” said Mike Sathekge, professor and head of the Nuclear Medicine Department at the University of Pretoria and Steve Biko Academic Hospital in Pretoria, South Africa. “In this study we sought to compare ²²⁵Ac-PSMA-617 to other common post-ADT treatments, such as chemotherapy, enzalutamide, and abiraterone acetate or docetaxel, administered in a comparable setting.”

The retrospective study included 53 patients who received ²²⁵Ac-PSMA-617 directly following ADT therapy. Molecular imaging with ⁶⁸Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for select patients to determine how much ²²⁵Ac-PSMA-617 to administer and for response assessment. Patients’ PSA levels were also obtained to assess response.

In the patients who experienced a PSA decline of more than 50 percent, the median PFS was 22 months, and the OS was not yet reached at the end of the study (55 months). For those with a PSA decline of less than 50 percent, the median PFS was four months, and the OS was nine months. In total, 48 patients (91 percent) had a PSA decline of more than 50 percent. Additionally, PET imaging became negative (showing no signs of disease) in 30 patients.

“It is clear that ²²⁵Ac-PSMA-617 is an effective treatment for men with mCRPC,” noted Sathekge. “This radioligand therapy may be a viable treatment option, especially if standard of care options are not available or are contraindicated. Since ²²⁵Ac-PSMA-617 has few treatment-related toxicities (notably xerostomia), it could also prove helpful in low middle income countries where patients are more likely to refuse chemotherapy or the current standard of care due to fear of side effects.”

This study was made available online in February 2022.

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The authors of “mCRPC patients receiving ²²⁵Ac-PSMA-617 therapy in post androgen deprivation therapy setting: Response to treatment and survival analysis” include Mike Sathekge and Ismaheel O. Lawal, Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa, and Nuclear Medicine Research Infrastructure, Pretoria, South Africa; Frank Bruchertseifer, European Commission, Joint Research Centre, Karlsruhe, Germany; Mariza Vorster, Johncy Mahapane, Cindy Davis, and Kgomotso Mokoala, Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa; Otto Knoesen, Nuclear Technology Products (NTP), Pelindaba, South Africa; Amanda Mdlophane, Nuclear Medicine Research Infrastructure, Pretoria, South Africa; Alex Maes, Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa, and Katholieke University Leuven, Kortrijk, Belgium; Christophe Van de Wiele, Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa, and Ghent University, Ghent, Belgium; and Alfred Morgenstern, Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa, and European Commission, Joint Research Centre, Karlsruhe, Germany.

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