PMID- 18725648 OWN - NLM STAT- MEDLINE DCOM- 20081027 LR - 20220316 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 26 IP - 30 DP - 2008 Oct 20 TI - Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. PG - 4875-82 LID - 10.1200/JCO.2008.16.3832 [doi] AB - PURPOSE: Adjuvant aromatase inhibitor therapy is well established in postmenopausal women with hormone receptor-positive breast cancer, but such therapy is complicated by accelerated bone loss and increased fracture risk. We investigated the ability of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, to protect against aromatase inhibitor-induced bone loss. PATIENTS AND METHODS: Eligible women with hormone receptor-positive nonmetastatic breast cancer treated with adjuvant aromatase inhibitor therapy were stratified by duration of aromatase inhibitor therapy (< or = 6 v > 6 months), received supplemental calcium and vitamin D, and were randomly assigned to receive placebo (n = 125) or subcutaneous denosumab 60 mg (n = 127) every 6 months. At enrollment, all patients were required to have evidence of low bone mass, excluding osteoporosis. The primary end point was percentage change from baseline at month 12 in lumbar spine bone mineral density (BMD). RESULTS: At 12 and 24 months, lumbar spine BMD increased by 5.5% and 7.6%, respectively, in the denosumab group versus placebo (P < .0001 at both time points). Increases were observed as early as 1 month and were not influenced by duration of aromatase inhibitor therapy. Increases in BMD were also observed at the total hip, total body, femoral neck, and the predominantly cortical one-third radius. Bone turnover markers decreased with denosumab treatment. Overall incidence of treatment-emergent adverse events (AEs) was similar between treatment groups. CONCLUSION: In women with nonmetastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy, twice-yearly administration of denosumab led to significant increases in BMD over 24 months at trabecular and cortical bone, with overall AE rates similar to those of placebo. FAU - Ellis, Georgiana K AU - Ellis GK AD - Seattle Cancer Care Alliance, Seattle, WA 98109-1023, USA. gellis@u.washington.edu FAU - Bone, Henry G AU - Bone HG FAU - Chlebowski, Rowan AU - Chlebowski R FAU - Paul, Devchand AU - Paul D FAU - Spadafora, Silvana AU - Spadafora S FAU - Smith, Judy AU - Smith J FAU - Fan, Michelle AU - Fan M FAU - Jun, Susie AU - Jun S LA - eng SI - ClinicalTrials.gov/NCT00089661 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20080825 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Aromatase Inhibitors) RN - 0 (RANK Ligand) RN - 4EQZ6YO2HI (Denosumab) SB - IM CIN - J Clin Oncol. 2008 Oct 20;26(30):4859-61. PMID: 18725646 MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/*administration & dosage MH - Antibodies, Monoclonal, Humanized MH - Aromatase Inhibitors/adverse effects MH - Bone Density/*drug effects MH - Breast Neoplasms/*drug therapy/epidemiology MH - Chemotherapy, Adjuvant MH - Comorbidity MH - Denosumab MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Fractures, Bone/epidemiology/prevention & control MH - Humans MH - Incidence MH - Middle Aged MH - Osteoporosis/chemically induced/epidemiology/*prevention & control MH - RANK Ligand/*administration & dosage EDAT- 2008/08/30 09:00 MHDA- 2008/10/28 09:00 CRDT- 2008/08/30 09:00 PHST- 2008/08/30 09:00 [pubmed] PHST- 2008/10/28 09:00 [medline] PHST- 2008/08/30 09:00 [entrez] AID - JCO.2008.16.3832 [pii] AID - 10.1200/JCO.2008.16.3832 [doi] PST - ppublish SO - J Clin Oncol. 2008 Oct 20;26(30):4875-82. doi: 10.1200/JCO.2008.16.3832. Epub 2008 Aug 25.