Efficacy and Safety of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer Patients

Abstract

Purpose The aim of this study was to evaluate the efficacy and safety of 177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). Methods In this prospective, single-arm, single-institutional study, 90 mCRPC patients with progressive disease (PD) on second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic 68Ga-PSMA-HBED-CC PET/CT, prior to inclusion for therapy. Included patients underwent 177Lu-PSMA-617 therapy at 8- to 12-weekly intervals. The primary end point was to assess the overall survival. The secondary and cosecondary end points included biochemical response assessment as per the Prostate Cancer Working Group 3 criteria, progression-free survival, radiological and molecular response criteria, clinical response, safety profile, and disease control rates. All the outcome parameters were evaluated in 90 patients except for the radiographic and molecular response, which was evaluated in 69 patients. Results The median age of patients was 66.5 years (range, 30–88 years). The median activity administered per cycle was 3.7 to 8 GBq ranging from 1 to 7 cycles, and patients were followed up over a median duration of 28 months. At 2- to 3-month interval after the first therapy and the end of the assessment, greater than 50% decline in prostate-specific antigen was observed in 32.2% and 45.5%, respectively. Univariate analysis did not reveal any variables such as prior therapies, laboratory parameters, concomitant hormonal therapy, and SUV patient parameters associated with prostate-specific antigen decline. Radiographic response by diagnostic CT revealed partial remission in 23% (16/69), stable disease in 54% (37/69), and PD in 23% (16/69) of patients. Molecular tumor response by PET Response Criteria in Solid Tumor 1 criteria revealed 19 (27.5%) of 69 patients with partial remission, 30 (43.5%) of 69 with stable disease, and 20 (29%) of 69 with PD. The disease control rates according to the radiographic and molecular response were 77% and 71%, respectively. The median overall survival and median progression-free survivals were 14 and 11.8 months, respectively. Toxicities related to radioligand therapy were low and transient with no serious adverse effects. Conclusions 177Lu-PSMA-617 radionuclide therapy is a safe and effective approach to the treatment of mCRPC patients.

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

“…Several studies have identified a link between the use of opioid pain medications and lower rates of PSA decline [11,12,23]. Similarly, in a prospective study of 90 patients, multivariate regression analysis showed that higher Eastern Cooperative Oncology Group (ECOG) score was associated with worse survival (HR: 10.69) [16].…”

“…Several studies have identified a link between the use of opioid pain medications and lower rates of PSA decline [ 11 , 12 , 23 ]. Similarly, in a prospective study of 90 patients, multivariate regression analysis showed that higher Eastern Cooperative Oncology Group (ECOG) score was associated with worse survival (HR: 10.69) [ 16 ]. Reflecting high tumor grade, elevated alkaline phosphatase, Gleason score of 10 or higher, and the presence of visceral metastases have been reported to be negative predictors of PSA response [ 7 , 12 ].…”

“…It is less clear whether low PSMA expression levels result in reduced responsiveness to therapy by way of lower levels of targetable substrate. Many studies have excluded patients with poor PSMA expression on imaging, even studies that have attempted to correlate standardized uptake value (SUV) scores with PSA decline [ 14 - 16 ]. Consequently, studies that have shown no relationship between SUV scores and PSA decline have primarily included patients with high PSMA expression based on PET imaging.…”

“…The mean dose was 6 GBq. In the largest prospective study to date, Yadav et al examined 90 patients with progressive mCRPC[16]. Participants underwent a median of four cycles, with eight-week intervals.…”

Explorative analysis of a predictive score for patients with metastatic, castration resistant prostate cancer undergoing radioligand therapy with [177Lu]Lu-labeled prostate-specific membrane antigen

“…In the last decade, several treatment options for patients with metastatic, castrationresistant prostate cancer (mCRPC) were established, including abiraterone, enzalutamide, docetaxel and cabazitaxel [2]. More recently, radioligand therapy (RLT) with ( 177 Lu)Lu-labeled prostate-specific membrane antigen (PSMA) was developed and has shown promising results with regards to prostatespecific antigen (PSA) response rates and radiographic responses [3]. Retrospective as well as early prospective data confirmed the favourable safety profile of RLT [4,5].…”