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Bone targeted therapy and skeletal related events in the era of enzalutamide and abiraterone acetate for castration resistant prostate cancer with bone metastases

Prostate Cancer and Prostatic Diseases volume 24, pages 341–348 (2021)Cite this article

Subjects

Abstract

Background

In an era of multiple life-prolonging therapies for metastatic castration resistant prostate cancer (mCRPC), the optimal timing of initiation and duration of antiresorptive bone targeted therapy (BTT) to prevent skeletal related events (SREs) is unknown.

Methods

To assess practice patterns of BTT use and its associations with clinical outcomes in a high-volume center in the modern era of metastatic CRPC management, a retrospective cohort of patients treated for mCRPC with BM between 2007 and 2017 was identified from a single institutions clinical research database. Study endpoints included time from the diagnosis of CRPC to the onset of SRE or OS. Cox proportional hazards model assessed association of BTT use with time to first SRE and OS.

Results

In total, 249 patients were identified; median follow-up was 7.7 (95%CI: 5.7–10.2) years. On multivariable analysis, patients with 4 or more BM at diagnosis of mCRPC who received BTT with abiraterone acetate or enzalutamide as first line therapy had a 42% reduced risk of developing an SRE (HR 0.58; 95%CI: 0.36–0.95) compared to those who never received BTT or received it in second line. No such effect was observed in patients with 1–3 BM. No OS difference was noted in patients who received BTT, whether with first line therapy or without. This study is limited by retrospective nature at a single institution.

Conclusions

Our hospital registry data indicate a potential benefit in terms of SRE prevention for early use of antiresorptive BTT in combination with life prolonging CRPC therapies for patients with CRPC and at least 4 BM.

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Fig. 1: Multivariable forrest plots for SRE and OS by disease volume.

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Acknowledgements

We thank Kevin Pels, PhD of Dana-Farber Cancer Institute for manuscript editing.

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Authors and Affiliations

  1. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Bradley McGregor, Kathryn P. Gray, Grace Shaw, Carolyn Evan, Edoardo Francini & Christopher Sweeney

  2. Northwest Medical Specialties, Gig Harbor, WA, USA

    Li Zhang

  3. Frontier Science Foundation, Boston, MA, USA

    Kathryn P. Gray

  4. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Edoardo Francini

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  1. Bradley McGregor
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Correspondence to Bradley McGregor.

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Conflict of interest

BM: discloses payment for consulting with Bayer, Astellas, Astra Zeneca, Seattle Genetics, Exelixis, Nektar, Pfizer, Janssen, Genentech, and EMD Serono. He received research support to Dana Farber Cancer Institute (DFCI) from Bristol Myers Squibb, Calithera, Exelixis, Seattle Genetics. C.S.: discloses a consulting or advisory at Sanofi, Janssen, Astellas Pharma, Bayer, Genentech, AstraZeneca, Pfizer, Lilly Celgene Research Funding: Janssen Biotech (Inst), Astellas Pharma (Inst), Sanofi (Inst), Bayer (Inst), Sotio (Inst), Dendreon (Inst). He has patents, Royalties, Other Intellectual Property for Pathenolide (Indiana University): dimethylaminoparthenolide (Leuchemix); Exelixis: Abiraterone plus cabozantinib combination. He owns stock in Leuchemix; LZ, KG, EF, GS, and CE report no conflict of interest.

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The study was performed in accordance with the Declaration of Helsinki; all patients were consented for their clinical data collection and the protocol was approved by DF/HCC IRB.

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McGregor, B., Zhang, L., Gray, K.P. et al. Bone targeted therapy and skeletal related events in the era of enzalutamide and abiraterone acetate for castration resistant prostate cancer with bone metastases. Prostate Cancer Prostatic Dis 24, 341–348 (2021). https://doi.org/10.1038/s41391-020-00280-6

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