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Symptomatic skeletal-related events in patients receiving longer term bone-modifying agents for bone metastases from breast and castration resistant prostate cancers

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Abstract

Background

The effect of longer-term use of bone-modifying agent (BMA) on symptomatic skeletal event (SSE) rates in patients with bone metastases remains unclear. This retrospective study of a cohort of patients in a randomized controlled trial evaluated SSEs in patients receiving BMAs at a single cancer center.

Methods

Data from patients with metastatic breast and castration-resistant prostate cancer (CRPC) were interrogated to evaluate the effects of longer-term use of BMAs on incidence, type, and risk factors for SSEs.

Results

Of 162 patients, 109 (67%) had breast cancer (BC) and 53 (33%) CRPC. Median age at diagnosis of bone metastases was 61.9 years (range 27.5–97.2) for BC patients and 72.1 (range 37.0–92.2) for CRPC patients. Median duration of BMA use was 2.3 years (range 0.1–9.9 years) for BC and 3.8 years (range 1.5–9.4) for CRPC patients. The initial BMAs in BC patients were pamidronate (46.8%), denosumab (31.2%), and zoledronate (22%). All CRPC patients received denosumab. During follow-up, 59% of BC and 75% of CRPC patients had at least one SSE. The number of patients experiencing ≥ 1 SSE per year was higher in the first year after bone metastasis diagnosis (63/162; 38.9%) compared with that in the second (26/149; 17.5%) and third years (30/123; 24.4%). Neither age, visceral disease, multiple bone metastases, nor biological markers for BC had a significant impact on time to first SSE.

Conclusions

The risk for SSEs was greatest in the first year after diagnosis of bone metastasis. Studies evaluating de-escalation and even stopping of BMAs with longer-term use may therefore be warranted.

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Data availability

De-identified dataset is available upon request and approval by the Ontario Cancer Research Ethics Board (OCREB 1–866-678–6427 Ext 6649).

Code availability

N/A.

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Acknowledgements

We are grateful to the Ottawa Hospital patients for their participation in the REaCT-BTA study.

Funding

The research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This work was supported by the Rethinking Clinical Trials (REaCT) Program platform at the Ottawa Hospital which is supported by The Ottawa Hospital Foundation and its generous donors.

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Authors and Affiliations

  1. Department of Medicine, Division of Medical Oncology, The Ottawa Hospital, University of Ottawa, 501 Smyth Road, Ottawa, Canada

    Mashari Alzahrani, Arif Awan, Terry L. Ng, Bader Alshamsan & Mark Clemons

  2. Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, Canada

    Carol Stober, Michelle Liu, Lisa Vandermeer & Mark Clemons

  3. Department of Oncology, McMaster University, Hamilton, Canada

    Gregory Pond

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  1. Mashari Alzahrani
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Contributions

MA, AA, CS, LV, and MC designed the study and prepared the protocol. MA and CS collected the data and coordinated the study, and GP did the statistical analysis. All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. MA, GP, AA, CS, LV, ML, TN, and MC wrote the manuscript. All authors were involved in the critical review of the manuscript and approved the final version.

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Correspondence to Mark Clemons.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ontario Cancer Research Ethics Board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All data has been de-identified to protect the identities of subjects involved in the research.

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Integrated verbal consent was obtained from all trial participants included in the study.

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All participants consented to de-identified publication of aggregate study results.

Conflict of interest

AA reports personal fees (honoraria) from Apotex, Eli Lily, Exact Sciences, Exactis, Novartis, Pfizer, and Roche outside the submitted work. TN reports personal fees (honoraria) from ARIAD, Takeda, and Boehringer-Ingelheim, outside the submitted work. GRP reports personal fees (honoraria) from Astra-Zeneca and Merck outside the submitted work, as well as a family member who works for Roche and owns stock in Roche. All other authors declare no competing interests.

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Alzahrani, M., Stober, C., Liu, M. et al. Symptomatic skeletal-related events in patients receiving longer term bone-modifying agents for bone metastases from breast and castration resistant prostate cancers. Support Care Cancer 30, 3977–3984 (2022). https://doi.org/10.1007/s00520-021-06714-8

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