Lipton, A., Smith, M.R., Fizazi, K. et al. (8 more authors) (2016) Changes in Bone Turnover Marker Levels and Clinical Outcomes in Patients With Advanced Cancer and Bone Metastases Treated With Bone Antiresorptive Agents. Clinical Cancer Research, 22 (23). pp. 5713-5721. ISSN 1078-0432
Abstract
Purpose: Bone antiresorptive agents can significantly reduce bone turnover markers (BTMs) in patients with advanced cancer. We evaluated association of changes in BTMs with overall survival (OS), disease progression (DP), and disease progression in bone (DPB) in patients with advanced cancer and bone metastases following denosumab or zoledronic acid treatment. Experimental Design: This is an integrated analysis of patient-level data from three identically designed, blinded, phase III trials with patients randomized to subcutaneous denosumab or intravenous zoledronic acid. Levels of the BTMs urinary N-telopeptide (uNTx) and serum bone-specific alkaline phosphatase (sBSAP) measured at study entry and month 3 were analyzed. OS, DP, and DPB were compared in patients with BTMs {greater than or equal to} median vs < median based on month 3 assessments. Results: uNTx levels {greater than or equal to} the median of 10.0 nmol/mmol at month 3 were associated with significantly reduced OS compared with levels < median (HR for death 1.85, P<0.0001). sBSAP levels {greater than or equal to} median of 12.6 ng/mL were associated with significantly reduced OS compared with levels < median (HR 2.44, P<0.0001). uNTx and sBSAP levels {greater than or equal to} median at month 3 were associated with significantly greater risk of DP (HR 1.31, P<0.0001 and HR 1.71, P<0.0001, respectively) and DPB (HR 1.11, P=0.0407 and HR 1.27, P<0.0001, respectively). Conclusions: BTM levels {greater than or equal to} median after 3 months of bone antiresorptive treatment were associated with reduced OS and increased risk of DP and DPB. Assessment of uNTx and sBSAP levels after bone antiresorptive therapy may add to identification of patients at risk for worse clinical outcomes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 American Association for Cancer Research. This is an author produced version of a paper subsequently published in Clinical Cancer Research. Uploaded in accordance with the publisher's self-archiving policy |
Keywords: | Bone-specific alkaline phosphatase; bone turnover marker; denosumab; overall survival; urinary N-telopeptide |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Jul 2016 15:16 |
Last Modified: | 18 Jul 2017 04:34 |
Published Version: | https://dx.doi.org/10.1158/1078-0432.CCR-15-3086 |
Status: | Published |
Publisher: | American Association for Cancer Research |
Identification Number: | 10.1158/1078-0432.CCR-15-3086 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101659 |