Novel PSMA-targeted therapy highly active in mCRPC

Over 90% of patients with metastatic castration-resistant prostate cancer (mCRPC) who received the PSMA-targeted therapy ²²⁵Ac-PSMA-617 had a 50% or greater reduction in their PSA level, according to study findings published online in The Journal of Nuclear Medicine.^1,2

All patients received ²²⁵Ac-PSMA-617 directly following androgen deprivation therapy. Overall, investigators observed the ≥50% PSA decline in 48 (91%) of 53 patients. The median progression-free survival was 22 months in these patients compared with only 4 months among patients who had a <50% PSA decline. At a follow-up time of 55 months, the median overall survival had not yet been reached in the ≥50% PSA decline group compared with 9 months in the <50% decline group.

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

The median age of the 53 patients was 63.4 years (range, 45-83). Forty-two patients had an ECOG performance status of 0 or 1, and the other 11 patients had ECOG performance status of 2. The median PSA level at baseline was 466 mg/ml. Forty-seven patients had bone metastases, 36 had lymph node metastases, and 6 had visceral metastases. Prior local therapy to the prostate included prostatectomy (31 patients) and radiation therapy (11 patients). Eleven patients had no prior local therapy.

All patients received ⁶⁸Ga-PSMA PET/CT molecular imaging at baseline and before every treatment. The median number of ²²⁵Ac-PSMA-617 cycles received was 3 (range, 1-7).

Across the study population, 96% of patients (51/53) had at least some decline in their PSA level in response to treatment. Further, 30 patients had negative PET imaging, meaning they showed no signs of disease.

Regarding safety, the most frequently reported adverse event was grade 1/2 xerostomia in 81% of patients. The investigators observed no cases of severe hematotoxicity. Grade 3/4 nephrotoxicity was only experienced by 3 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.”

References

1. Novel Radioligand Therapy Proven Superior for Metastatic Prostate Cancer Patients. Published online March 9, 2022. Accessed March 14, 2022. https://bit.ly/3pZo5Kf.

2. Sathekge M, Bruchertseifer F, Vorster. mCRPC patients receiving 225 Ac-PSMA-617 therapy in post androgen deprivation therapy setting: Response to treatment and survival analysis [published online ahead of print February 17, 2022]. J Nucl Med. doi: 10.2967/jnumed.121.263618.