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

  • Curr Oncol Rep. 2021 Mar 29;23(5):59. doi: 10.1007/s11912-021-01042-w.
Michael Sun  1 ,  Muhammad Junaid Niaz  2 ,  Muhammad Obaid Niaz  3 ,  Scott T Tagawa  4  5  6
Affiliations
  • 1. Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, 525 East 68th Street, Box 403, New York, NY, 10065, USA.
  • 2. Department of Urology, Weill Cornell Medicine, New York, NY, USA.
  • 3. Sharif Medical City Hospital, Lahore, Pakistan.
  • 4. Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, 525 East 68th Street, Box 403, New York, NY, 10065, USA. [email protected].
  • 5. Department of Urology, Weill Cornell Medicine, New York, NY, USA. [email protected].
  • 6. Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. [email protected].
PMID: 33778927 DOI: 10.1007/s11912-021-01042-w
Abstract

Purpose of review: 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.

Recent findings: 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.

Keywords
Metastatic castration resistant prostate cancer; Monoclonal antibodies; Prostate specific membrane antigen; Radioligand therapy; Small molecules; Targeted therapies.
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