Changes in bone turnover marker levels and clinical outcomes in patients with advanced cancer and bone metastases treated with bone antiresorptive agents

Allan Lipton, Matthew R. Smith, Karim Fizazi, Alison T Stopeck, David Henry, Janet E. Brown, Neal D. Shore, Fred Saad, Andrew Spencer, Li Zhu, Douglas J. Warner

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: Bone antiresorptive agents can significantly reduce bone turnover markers (BTM) 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 ≥ median versus < median based on month 3 assessments. Results: uNTx levels ≥ 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 ≥ 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 ≥l 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-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.

Original languageEnglish (US)
Pages (from-to)5713-5721
Number of pages9
JournalClinical Cancer Research
Volume22
Issue number23
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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Bone Density Conservation Agents
Bone Neoplasms
Bone Remodeling
Biomarkers
Neoplasm Metastasis
Bone and Bones
Disease Progression
zoledronic acid
Alkaline Phosphatase
Survival
Serum
Research Design
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Changes in bone turnover marker levels and clinical outcomes in patients with advanced cancer and bone metastases treated with bone antiresorptive agents. / Lipton, Allan; Smith, Matthew R.; Fizazi, Karim; Stopeck, Alison T; Henry, David; Brown, Janet E.; Shore, Neal D.; Saad, Fred; Spencer, Andrew; Zhu, Li; Warner, Douglas J.

In: Clinical Cancer Research, Vol. 22, No. 23, 01.12.2016, p. 5713-5721.

Research output: Contribution to journalArticle

Lipton, Allan ; Smith, Matthew R. ; Fizazi, Karim ; Stopeck, Alison T ; Henry, David ; Brown, Janet E. ; Shore, Neal D. ; Saad, Fred ; Spencer, Andrew ; Zhu, Li ; Warner, Douglas J. / Changes in bone turnover marker levels and clinical outcomes in patients with advanced cancer and bone metastases treated with bone antiresorptive agents. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 23. pp. 5713-5721.
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abstract = "Purpose: Bone antiresorptive agents can significantly reduce bone turnover markers (BTM) 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 ≥ median versus < median based on month 3 assessments. Results: uNTx levels ≥ 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 ≥ 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 ≥l 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-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.",
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T1 - Changes in bone turnover marker levels and clinical outcomes in patients with advanced cancer and bone metastases treated with bone antiresorptive agents

AU - Lipton, Allan

AU - Smith, Matthew R.

AU - Fizazi, Karim

AU - Stopeck, Alison T

AU - Henry, David

AU - Brown, Janet E.

AU - Shore, Neal D.

AU - Saad, Fred

AU - Spencer, Andrew

AU - Zhu, Li

AU - Warner, Douglas J.

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N2 - Purpose: Bone antiresorptive agents can significantly reduce bone turnover markers (BTM) 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 ≥ median versus < median based on month 3 assessments. Results: uNTx levels ≥ 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 ≥ 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 ≥l 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-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.

AB - Purpose: Bone antiresorptive agents can significantly reduce bone turnover markers (BTM) 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 ≥ median versus < median based on month 3 assessments. Results: uNTx levels ≥ 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 ≥ 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 ≥l 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-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.

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