The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial.
25-OH-vitamin D, 25-hydroxyvitamin D
Art, antiresorptive therapy
BSAP, bone-specific alkaline phosphatase
Bone health
Bone marker
Breast cancer
CI, confidence interval
CR, complete response
CTX, C-terminal cross-linking telopeptide of type 1 collagen
Everolimus
HER2-negative, human epidermal growth factor receptor 2-negative
HR, hazard ratio
HR +, hormone receptor-positive
Hormone receptor-positive
Mammalian target of rapamycin
NSAI, non-steroidal aromatase inhibitor
OR, overall response
ORR, overall response rate
ORR24w, overall response rate within the first 24 weeks of treatment
P1NP, procollagen type 1 N-terminal peptide
PFS, progression-free survival
PR, partial response
PTH, parathyroid hormone
SD, standard deviation
SRE, skeletal-related event
mTOR, mammalian target of rapamycin
Journal
Journal of bone oncology
ISSN: 2212-1366
Titre abrégé: J Bone Oncol
Pays: Netherlands
ID NLM: 101610292
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
07
08
2018
revised:
26
09
2018
accepted:
26
09
2018
entrez:
6
12
2018
pubmed:
6
12
2018
medline:
6
12
2018
Statut:
epublish
Résumé
Breast cancer and its treatments are associated with a detrimental effect on bone health. Here we report the results of an exploratory analysis assessing changes in levels of biomarkers of bone metabolism in patients enrolled in the phase IIIb 4EVER study. The 4EVER trial investigated everolimus in combination with exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. In this prespecified exploratory analysis, changes in biomarkers of bone turnover were assessed in patients from baseline to weeks 4, 12, and 24. The serum bone markers assessed were procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25-OH-vitamin D). On-treatment changes in bone markers over time were described per subgroup of interest and efficacy outcomes. Bone marker data were available for 241 of 299 enrolled patients. At the final assessment, P1NP, osteocalcin, PTH, 25-OH-vitamin D (all These exploratory analyses support use of everolimus plus exemestane for the treatment of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, and add to the body of evidence suggesting a potentially favorable impact of everolimus on bone turnover. NCT01626222.
Sections du résumé
BACKGROUND
BACKGROUND
Breast cancer and its treatments are associated with a detrimental effect on bone health. Here we report the results of an exploratory analysis assessing changes in levels of biomarkers of bone metabolism in patients enrolled in the phase IIIb 4EVER study.
METHODS
METHODS
The 4EVER trial investigated everolimus in combination with exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. In this prespecified exploratory analysis, changes in biomarkers of bone turnover were assessed in patients from baseline to weeks 4, 12, and 24. The serum bone markers assessed were procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25-OH-vitamin D). On-treatment changes in bone markers over time were described per subgroup of interest and efficacy outcomes.
RESULTS
RESULTS
Bone marker data were available for 241 of 299 enrolled patients. At the final assessment, P1NP, osteocalcin, PTH, 25-OH-vitamin D (all
CONCLUSIONS
CONCLUSIONS
These exploratory analyses support use of everolimus plus exemestane for the treatment of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, and add to the body of evidence suggesting a potentially favorable impact of everolimus on bone turnover.
TRIAL REGISTRATION
BACKGROUND
NCT01626222.
Identifiants
pubmed: 30515367
doi: 10.1016/j.jbo.2018.09.010
pii: S2212-1374(18)30113-1
pii: 100199
pmc: PMC6263089
doi:
Banques de données
ClinicalTrials.gov
['NCT01626222']
Types de publication
Journal Article
Langues
eng
Pagination
010-10Références
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