A novel prostate cancer treatment—actinium Ac-225–PSMA-617 radioligand therapy—has been shown to increase the progression-free and overall survival of patients with metastatic castration-resistant prostate cancer, according to research published by Sathekge et al in the Journal of Nuclear Medicine. Ninety-one percent of patients experienced a greater than 50% reduction of their initial prostate-specific antigen (PSA) value after treatment with Ac-225–PSMA-617, resulting in a progression-free survival rate of 22 months and an overall survival rate that was not yet reached at the conclusion of the study.
Although the 5-year survival rate for patients with localized prostate cancer is nearly 100%, for those with metastatic castration-resistant disease, it is only 30%. Clinical studies have demonstrated the efficacy and safety of several therapies, including lutetium Lu-177–PSMA-617 in the post–androgen deprivation therapy (ADT) setting in patients with metastatic castration-resistant prostate cancer. Additional therapies are often considered once the disease begins to progress again.
“Previous research has shown a remarkable therapeutic efficacy of [Ac-225]–PSMA-617 in heavily pretreated [patients with] metastatic castration-resistant prostate cancer…,” said Mike Sathekge, MBChB, MMed, PhD, 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 [Ac-225]–PSMA-617 to other common post-ADT treatments, such as chemotherapy, enzalutamide, and abiraterone acetate or docetaxel, administered in a comparable setting.”
Study Details
The retrospective study included 53 patients who received Ac-225–PSMA-617 directly following ADT therapy. Molecular imaging with gallium Ga-68–PSMA positron-emission tomography (PET)/computed tomography was obtained at baseline, before every treatment cycle, and on follow-up for select patients to determine how much radioligand therapy 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%, median progression-free survival was 22 months, and overall survival was not yet reached at the end of the study (55 months). For those with a PSA decline of less than 50%, median progression-free survival was 4 months and overall survival was 9 months. In total, 48 patients (91%) had a PSA decline of more than 50%. Additionally, PET imaging became negative (showing no signs of disease) in 30 patients.
“It is clear that [Ac-225]–PSMA-617 is an effective treatment for men with metastatic castration-resistant prostate cancer,” noted Dr. Sathekge. “This radioligand therapy may be a viable treatment option, especially if standard-of-care options are not available or are contraindicated. Since [Ac-255]–PSMA-617 has few treatment-related toxicities (notably xerostomia), it could also prove helpful in low- [and] middle-income countries where patients are more likely to refuse chemotherapy or the current standard of care due to fear of side effects.”
Disclosure: For full disclosures of the study authors, visit jnm.snmjournals.org.
