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MINI REVIEW article

Front. Med.
Sec. Nuclear Medicine
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1460212

Treatment intensification with radium-223 plus enzalutamide in patients with metastatic castration-resistant prostate cancer

Provisionally accepted
Neal Shore Neal Shore 1Joan Carles Joan Carles 2Ray McDermott Ray McDermott 3Neeraj Agarwal Neeraj Agarwal 4Bertrand TOMBAL Bertrand TOMBAL 5*
  • 1 Carolina Urologic Research Center, Myrtle Beach, SC, United States
  • 2 Vall d'Hebron University Hospital, Barcelona, Catalonia, Spain
  • 3 St Vincent's University Hospital, Cancer Trials Ireland, Dublin, Ireland
  • 4 Huntsman Cancer Institute, School of Medicine, The University of Utah, Salt Lake City, Utah, United States
  • 5 Cliniques Universitaires Sait Luc, Brussels, Belgium

The final, formatted version of the article will be published soon.

    Several life-prolonging therapies with diverse mechanisms of action (MoA) are available for the treatment of metastatic castrationhormone-sensitive/castration-resistant prostate cancer, with many patients requiring multiple lines of therapy. Nevertheless, treatment optimization to further delay disease progression and improve overall survival remains an unmet need. Despite the number of agents with differing MoAs approved for advanced prostate cancer, many patients receive only one or two life-prolonging therapies. One strategy for enhancing the benefit of treatment for this aggressive disease is combining therapies with different MoAs (treatment intensification) early in the disease course, which may be more effective than administering therapies sequentially, yet still allow for subsequent sequential use of individual therapies to optimize patient outcomes. In this narrative review we discuss the rationale for combining 223 radium dichloride ( 223 Ra; an alpha-emitting radionuclide) with enzalutamide (an androgen receptor inhibitor) for treatment intensification, including their differing MoAs, their individual efficacy in this setting, and their largely nonoverlapping tolerability profiles. We also summarize the preclinical and clinical data available for this combination to date, including interim safety data from the phase 3 EORTC 1333/PEACE III study which highlight the low fracture risk of 223 Ra plus enzalutamide when administered concomitantly with bone health agents. Relevant data were sourced from clinical studies published by the authors and via searches of PubMed, clinical trial registries and congress abstracts.

    Keywords: radium-223, metastatic castration-resistant prostate cancer, enzalutamide, Treatment intensification, combination therapy

    Received: 05 Jul 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Shore, Carles, McDermott, Agarwal and TOMBAL. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Bertrand TOMBAL, Cliniques Universitaires Sait Luc, Brussels, Belgium

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.