225Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings

Abstract

Purpose 225Ac-PSMA-617 has demonstrated good anti-tumor effect as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. No study has previously assessed treatment outcome and survival following 225Ac-PSMA-617 treatment of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) patients. Based on the potential side effects that are known and explained to the patients by the oncologist, some of the patients refused the standard treatment and are seeking alternative therapies. Thus, we report our preliminary findings in a retrospective series of 21 mHSPC patients that refused standard treatment options and were treated with 225Ac-PSMA-617. Methods We retrospectively reviewed patients with histologically confirmed de novo treatment-naïve bone ± visceral mHSPC that were treated with 225Ac-PSMA-617 radioligand therapy (RLT). Inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, treatment-naive bone ± visceral mHSPC, and patients refusal for ADT ± docetaxel, abiraterone acetate, or enzalutamide. We evaluated the response to treatment using prostate-specific antigen (PSA) response and the progression-free survival (PFS) and overall survival (OS) as well as the toxicities. Results Twenty-one mHSPC patients were included in this preliminary work. Following treatment, twenty patients (95%) had any decline in PSA and eighteen patients (86%) presented with a PSA decline of ≥ 50% including 4 patients in whom PSA became undetectable. A lower percentage decrease in PSA following treatment was associated with increased mortality and shorter progression-free survival. Overall, administration of 225Ac-PSMA-617 was well tolerated. The commonest toxicity seen was grade I/II dry mouth observed in 94% of patients. Conclusions Given these favorable results, randomized prospective multicenter trials assessing the clinical value of 225Ac-PSMA-617 as a therapeutic agent for mHSPC administered either as monotherapy or administered concomitant with ADT are of interest.

PSMA Radioligand Therapy in Prostate Cancer

“…Multivariate analysis showed that PSA declines correlated with OS and progression-free survival (PFS) ( P = 0.003 and P = 0.015, respectively). Sathekge et al 19 found median global OS shorter than those obtained in CHAARTED (31 vs 57.6 months) and LATITUDE (38% vs 66% after 3 years) studies. These 3 clinical trials treated patients with 225 Ac-PSMA-617, ADT plus docetaxel, and ADT plus AA/P, respectively 7,11,19,20 …”

“…Sathekge et al 19 found median global OS shorter than those obtained in CHAARTED (31 vs 57.6 months) and LATITUDE (38% vs 66% after 3 years) studies. These 3 clinical trials treated patients with 225 Ac-PSMA-617, ADT plus docetaxel, and ADT plus AA/P, respectively 7,11,19,20 …”

“…These 3 clinical trials treated patients with 225 Ac-PSMA-617, ADT plus docetaxel, and ADT plus AA/P, respectively. 7,11,19,20 UPFrontPSMA is an ongoing clinical trial comparing the efficacy of 177 Lu-PSMA-617 followed by docetaxel + ADT versus docetaxel + ADT alone in newly diagnosed high-volume metastatic castration-sensitive prostate cancer (mCSPC). 18 F-PET/CT will be used in addition to 68 Ga-PSMA PET/CT.…”

“…A retrospective study by Sathekge et al 19 evaluated the treatment response to 225 Ac-PSMA-617 in metastatic de novo prostate cancer patients who had a mixed pool of disease volumes. Multivariate analysis showed that PSA declines correlated with OS and progression-free survival (PFS) ( P = 0.003 and P = 0.015, respectively).…”

Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine

“…Outside Japan, 225 Ac has attracted attention in alpha-ray nuclear medicine therapy, and clinical trials are underway [27][28][29]. We are also investigating the use of 225 Ac, but there are still problems with its application in medicine, such as the lack of a mass production method in Japan.…”