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

  • Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)
  • Published:
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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.

Summary

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.

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Authors and 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

    Michael Sun & Scott T. Tagawa

  2. Department of Urology, Weill Cornell Medicine, New York, NY, USA

    Muhammad Junaid Niaz & Scott T. Tagawa

  3. Sharif Medical City Hospital, Lahore, Pakistan

    Muhammad Obaid Niaz

  4. Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA

    Scott T. Tagawa

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  1. Michael Sun
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  2. Muhammad Junaid Niaz
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Correspondence to Scott T. Tagawa.

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Michael Sun, Muhammad Junaid Niaz, and Muhammad Obaid Niaz declare no conflict of interest. Weill Cornell Medicine has received research funding for trials led by Scott T. Tagawa from Novartis/Advanced Accelerator Applications, Bayer, POINT Biopharma, Amgen, Atlab, Progenics, Pfizer, Clovis Oncology, Janssen, Seattle Genetics, Immunomedics, Ambrx, Inovio, Sanofi, Merck, Karyopharm, AbbVie, AstraZeneca, and Bristol-Myers Squibb; and he has received compensation for service as a consultant from Novartis/Advanced Accelerator Applications, Bayer, Blue Earth Diagnostics, POINT Biopharma, Amgen, Pfizer, QED, Clovis Oncology, Janssen, Seattle Genetics, Immunomedics, Ambrx, Sanofi, Karyopharm, and AbbVie.

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Sun, M., Niaz, M.J., Niaz, M.O. et al. Prostate-Specific Membrane Antigen (PSMA)-Targeted Radionuclide Therapies for Prostate Cancer. Curr Oncol Rep 23, 59 (2021). https://doi.org/10.1007/s11912-021-01042-w

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