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

被引:275
作者
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
机构
[1] Milton S Hershey Med Ctr Oncol, Hershey, PA 17033 USA
[2] Univ Klin Innere Med, Vienna, Austria
[3] Hosp Gen Mexico City, Mexico City, DF, Mexico
[4] Hosp Juarez Mexico, Mexico City, DF, Mexico
[5] Clin Victor Bordet, Le Mans, France
[6] Inst Jules Bordet, B-1000 Brussels, Belgium
[7] Western Hosp, Footscray, Vic, Australia
[8] Univ Politecn Marche, Ancona, Italy
[9] Hosp Clin Barcelona, Barcelona, Spain
[10] Cross Canc Ctr, Edmonton, AB, Canada
[11] Tom Baker Canc Clin, Calgary, AB, Canada
[12] Weston Pk Hosp, Sheffield, S Yorkshire, England
[13] Amgen Inc, Thousand Oaks, CA 91320 USA
关键词
D O I
10.1200/JCO.2007.11.8604
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-kappa B 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.
引用
收藏
页码:4431 / 4437
页数:7
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