Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases

Allan Lipton, Guenther G. Steger, Jazmin Figueroa, Cristina Alvarado, Philippe Solal-Celigny, Jean Jacques Body, Richard De Boer, Rossana Berardi, Pere Gascon, Katia S. Tonkin, Robert Coleman, Alexander H.G. Paterson, Mark C. Peterson, Michelle Fan, Amy Kinsey, Susie Jun

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Abstract

Purpose: Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-κB ligand, suppresses bone resorption. In this study, we evaluated the efficacy and safety of five dosing regimens of denosumab in patients with breast cancer-related bone metastases not previously treated with intravenous bisphosphonates (IV BPs). Patients and Methods: Eligible women (n = 255) with breast cancer-related bone metastases were stratified by type of antineoplastic therapy received and randomly assigned to one of six cohorts (five denosumab cohorts [blinded to dose and frequency]; one open-label IV BP cohort). Denosumab was administered subcutaneously every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg). The primary end point was percentage of change in the bone turnover marker urine N-telopeptide corrected for urine creatinine (uNTx/Cr) from baseline to study week 13. The percentage of patients achieving more than 65% uNTx/Cr reduction, time to more than 65% uNTx/Cr reduction, patients experiencing one or more on-study skeletal-related events (SRE), and safety were also evaluated. Results: At study week 13, the median percent reduction in uNTx/Cr was 71% for the pooled denosumab groups and 79% for the IV BP group. Overall, 74% of denosumab-treated patients (157 of 211) achieved a more than 65% reduction in uNTx/Cr compared with 63% of bisphosphonate-treated patients (27 of 43). On-study SREs were experienced by 9% of denosumab-treated patients (20 of 211) versus 16% of bisphosphonate-treated patients (seven of 43). No serious or fatal adverse events related to denosumab occurred. Conclusion: Subcutaneous denosumab may be similar to IV BPs in suppressing bone turnover and reducing SRE risk. The safety profile was consistent with an advanced breast cancer population receiving systemic therapy.

Original languageEnglish (US)
Pages (from-to)4431-4437
Number of pages7
JournalJournal of Clinical Oncology
Volume25
Issue number28
DOIs
StatePublished - Oct 1 2007

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Bone Neoplasms
Patient Safety
Diphosphonates
Breast Neoplasms
Neoplasm Metastasis
Bone Remodeling
Safety
Urine
Denosumab
Bone Resorption
Cytoplasmic and Nuclear Receptors
Antineoplastic Agents
Creatinine
Monoclonal Antibodies
Ligands

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lipton, Allan ; Steger, Guenther G. ; Figueroa, Jazmin ; Alvarado, Cristina ; Solal-Celigny, Philippe ; Body, Jean Jacques ; De Boer, Richard ; Berardi, Rossana ; Gascon, Pere ; Tonkin, Katia S. ; Coleman, Robert ; Paterson, Alexander H.G. ; Peterson, Mark C. ; Fan, Michelle ; Kinsey, Amy ; Jun, Susie. / Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 28. pp. 4431-4437.
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title = "Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases",
abstract = "Purpose: Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-κB ligand, suppresses bone resorption. In this study, we evaluated the efficacy and safety of five dosing regimens of denosumab in patients with breast cancer-related bone metastases not previously treated with intravenous bisphosphonates (IV BPs). Patients and Methods: Eligible women (n = 255) with breast cancer-related bone metastases were stratified by type of antineoplastic therapy received and randomly assigned to one of six cohorts (five denosumab cohorts [blinded to dose and frequency]; one open-label IV BP cohort). Denosumab was administered subcutaneously every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg). The primary end point was percentage of change in the bone turnover marker urine N-telopeptide corrected for urine creatinine (uNTx/Cr) from baseline to study week 13. The percentage of patients achieving more than 65{\%} uNTx/Cr reduction, time to more than 65{\%} uNTx/Cr reduction, patients experiencing one or more on-study skeletal-related events (SRE), and safety were also evaluated. Results: At study week 13, the median percent reduction in uNTx/Cr was 71{\%} for the pooled denosumab groups and 79{\%} for the IV BP group. Overall, 74{\%} of denosumab-treated patients (157 of 211) achieved a more than 65{\%} reduction in uNTx/Cr compared with 63{\%} of bisphosphonate-treated patients (27 of 43). On-study SREs were experienced by 9{\%} of denosumab-treated patients (20 of 211) versus 16{\%} of bisphosphonate-treated patients (seven of 43). No serious or fatal adverse events related to denosumab occurred. Conclusion: Subcutaneous denosumab may be similar to IV BPs in suppressing bone turnover and reducing SRE risk. The safety profile was consistent with an advanced breast cancer population receiving systemic therapy.",
author = "Allan Lipton and Steger, {Guenther G.} and Jazmin Figueroa and Cristina Alvarado and Philippe Solal-Celigny and Body, {Jean Jacques} and {De Boer}, Richard and Rossana Berardi and Pere Gascon and Tonkin, {Katia S.} and Robert Coleman and Paterson, {Alexander H.G.} and Peterson, {Mark C.} and Michelle Fan and Amy Kinsey and Susie Jun",
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Lipton, A, Steger, GG, Figueroa, J, Alvarado, C, Solal-Celigny, P, Body, JJ, De Boer, R, Berardi, R, Gascon, P, Tonkin, KS, Coleman, R, Paterson, AHG, Peterson, MC, Fan, M, Kinsey, A & Jun, S 2007, 'Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases', Journal of Clinical Oncology, vol. 25, no. 28, pp. 4431-4437. https://doi.org/10.1200/JCO.2007.11.8604

Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. / Lipton, Allan; Steger, Guenther G.; Figueroa, Jazmin; Alvarado, Cristina; Solal-Celigny, Philippe; Body, Jean Jacques; De Boer, Richard; Berardi, Rossana; Gascon, Pere; Tonkin, Katia S.; Coleman, Robert; Paterson, Alexander H.G.; Peterson, Mark C.; Fan, Michelle; Kinsey, Amy; Jun, Susie.

In: Journal of Clinical Oncology, Vol. 25, No. 28, 01.10.2007, p. 4431-4437.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases

AU - Lipton, Allan

AU - Steger, Guenther G.

AU - Figueroa, Jazmin

AU - Alvarado, Cristina

AU - Solal-Celigny, Philippe

AU - Body, Jean Jacques

AU - De Boer, Richard

AU - Berardi, Rossana

AU - Gascon, Pere

AU - Tonkin, Katia S.

AU - Coleman, Robert

AU - Paterson, Alexander H.G.

AU - Peterson, Mark C.

AU - Fan, Michelle

AU - Kinsey, Amy

AU - Jun, Susie

PY - 2007/10/1

Y1 - 2007/10/1

N2 - Purpose: Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-κB ligand, suppresses bone resorption. In this study, we evaluated the efficacy and safety of five dosing regimens of denosumab in patients with breast cancer-related bone metastases not previously treated with intravenous bisphosphonates (IV BPs). Patients and Methods: Eligible women (n = 255) with breast cancer-related bone metastases were stratified by type of antineoplastic therapy received and randomly assigned to one of six cohorts (five denosumab cohorts [blinded to dose and frequency]; one open-label IV BP cohort). Denosumab was administered subcutaneously every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg). The primary end point was percentage of change in the bone turnover marker urine N-telopeptide corrected for urine creatinine (uNTx/Cr) from baseline to study week 13. The percentage of patients achieving more than 65% uNTx/Cr reduction, time to more than 65% uNTx/Cr reduction, patients experiencing one or more on-study skeletal-related events (SRE), and safety were also evaluated. Results: At study week 13, the median percent reduction in uNTx/Cr was 71% for the pooled denosumab groups and 79% for the IV BP group. Overall, 74% of denosumab-treated patients (157 of 211) achieved a more than 65% reduction in uNTx/Cr compared with 63% of bisphosphonate-treated patients (27 of 43). On-study SREs were experienced by 9% of denosumab-treated patients (20 of 211) versus 16% of bisphosphonate-treated patients (seven of 43). No serious or fatal adverse events related to denosumab occurred. Conclusion: Subcutaneous denosumab may be similar to IV BPs in suppressing bone turnover and reducing SRE risk. The safety profile was consistent with an advanced breast cancer population receiving systemic therapy.

AB - Purpose: Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-κB ligand, suppresses bone resorption. In this study, we evaluated the efficacy and safety of five dosing regimens of denosumab in patients with breast cancer-related bone metastases not previously treated with intravenous bisphosphonates (IV BPs). Patients and Methods: Eligible women (n = 255) with breast cancer-related bone metastases were stratified by type of antineoplastic therapy received and randomly assigned to one of six cohorts (five denosumab cohorts [blinded to dose and frequency]; one open-label IV BP cohort). Denosumab was administered subcutaneously every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg). The primary end point was percentage of change in the bone turnover marker urine N-telopeptide corrected for urine creatinine (uNTx/Cr) from baseline to study week 13. The percentage of patients achieving more than 65% uNTx/Cr reduction, time to more than 65% uNTx/Cr reduction, patients experiencing one or more on-study skeletal-related events (SRE), and safety were also evaluated. Results: At study week 13, the median percent reduction in uNTx/Cr was 71% for the pooled denosumab groups and 79% for the IV BP group. Overall, 74% of denosumab-treated patients (157 of 211) achieved a more than 65% reduction in uNTx/Cr compared with 63% of bisphosphonate-treated patients (27 of 43). On-study SREs were experienced by 9% of denosumab-treated patients (20 of 211) versus 16% of bisphosphonate-treated patients (seven of 43). No serious or fatal adverse events related to denosumab occurred. Conclusion: Subcutaneous denosumab may be similar to IV BPs in suppressing bone turnover and reducing SRE risk. The safety profile was consistent with an advanced breast cancer population receiving systemic therapy.

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