Prostate-Specific Membrane Antigen (PSMA)-Targeted Radionuclide Therapies for Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) is a promising investigational treatment for metastatic castration-resistant prostate cancer (mCRPC). This review describes the available data with PSMA TRT.

Conjugates used for PSMA TRT include antibodies or small molecules PSMA-radiolabeled with beta (most commonly 177Lu) or alpha emitters (commonly 225Ac). 177Lu-J591 demonstrated accurate targeting of known metastatic sites, based on post-treatment scintigraphy, in study populations that were not selected for PSMA expression, with evidence of dose-response and dose-limiting myelosuppression. Early phase studies of 177Lu-PSMA-617 have demonstrated favorable adverse event profiles and signs of clinical activity as evidenced by PSA responses and other short-term outcomes. A phase II randomized study of 177Lu-PSMA-617 showed a superior PSA50 response rate (66 vs 37%) over cabazitaxel in patients with docetaxel-pretreated, progressive mCRPC selected by PSMA and FDG PET/CT scans. PSMA TRT is emerging as a promising investigational therapy for mCRPC. The first randomized data with 177Lu-PSMA-617 (phase 2) have been presented, and the first phase 3 trial has completed accrual with radiographic progression-free and overall survival as dual primary endpoints. Multiple additional phase 3 trials of PSMA-TRT are starting and studies investigating optimal patient selection and combination therapy continue.

Current oncology reports. 2021 Mar 29*** epublish ***

Michael Sun, Muhammad Junaid Niaz, Muhammad Obaid Niaz, Scott T Tagawa

Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, 525 East 68th Street, Box 403, New York, NY, 10065, USA., Department of Urology, Weill Cornell Medicine, New York, NY, USA., Sharif Medical City Hospital, Lahore, Pakistan., Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, 525 East 68th Street, Box 403, New York, NY, 10065, USA. .