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Review
. 2024 Oct 24:11:1460212.
doi: 10.3389/fmed.2024.1460212. eCollection 2024.

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

Neal Shore  1 , Joan Carles  2 , Ray McDermott  3 , Neeraj Agarwal  4 , Bertrand Tombal  5
Affiliations
Review

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

Neal Shore et al. Front Med (Lausanne). .

Abstract

Several life-prolonging therapies with diverse mechanisms of action (MoA) are available for the treatment of metastatic hormone-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 223radium dichloride (223Ra; 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 non-overlapping 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 223Ra 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: combination therapy; enzalutamide; metastatic castration-resistant prostate cancer; radium-223; treatment intensification.

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Conflict of interest statement

Neal Shore: Consulting or advisory role: AbbVie, Alessa, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Clarity, Dendreon, Exact Imaging, Ferring, Foundation Medicine, Janssen, Lantheus, Lilly, Mdxhealth, Merck, Myovant, Myriad, Novartis, Pfizer, Photocure, Telix Tolmar, UroGen. Joan Carles: Consultant and scientific advisory board attendee: Amgen, Astellas, Bayer, Bristol-Myers Squibb, MSD, Johnson & Johnson, Sanofi, Pfizer, Novartis (AAA); Speaker bureau: Asofarma, Astellas, Bayer, Johnson & Johnson, Sanofi; Others: CAMDHA Agency Institutional Studies Collaborations: AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, Astellas Pharma, AstraZeneca, Aveo Pharmaceuticals, Bayer, Blueprint Medicines Corporation, BN Immunotherapeutics, Boehringer Ingelheim España, Bristol-Myers Squibb, Clovis Oncology, Cougar Biotechnology, Deciphera Pharmaceuticals, Exelixis, F. Hoffmann-La Roche, Genentech, GlaxoSmithKline, Incyte, Janssen-Cilag International, Karyopharm Therapeutics, Laboratoires Leurquin Mediolanum, Eli Lilly, Medimmune, Millennium Pharmaceuticals, Nanobiotix, Novartis, Pfizer, Puma Biotechnology, Sanofi-Aventis, SFJ Pharma, Teva Pharma. Ray McDermott: Consulting or advisory role: Bayer, Janssen, Pfizer; Support for travel and/or accommodation: Celgene, Janssen, Pfizer; Research funding related to clinical trials: Clovis Oncology, Amgen, Bayer, Bristol-Myers Squibb, Merck. Neeraj Agarwal: Honorarium before May 2021 and during his lifetime for consulting: Astellas, AstraZeneca, Aveo, Bayer, Bristol-Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, Seattle Genetics; Research funding (during his lifetime, to NA’s institution): Arnivas, Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol-Meyers Squibb, Calithera, Celldex, Clovis, CRISPR Therapeutics, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GlaxoSmithKline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, Tracon. Bertrand Tombal: Personal fees and nonfinancial support: Amgen, Astellas, Bayer, Ferring Pharmaceuticals, Janssen, Sanofi; Personal fees: Pfizer, Steba Biotech, Takeda; Grants: Ferring Pharmaceuticals. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Mechanism of action (MoA) of 223Ra and enzalutamide.
See this image and copyright information in PMC

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