RESUMEN
Denosumab increased lumbar spine bone mineral density (BMD) versus placebo in a 2-year, randomized, placebo-controlled, phase 3 study of patients with hormone-receptor-positive, non-metastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy. In subgroup analyses at 12 and 24 months, we evaluated factors (duration and type of aromatase inhibitor, tamoxifen use, age, time since menopause, body mass index, T-score) that might influence BMD at the lumbar spine, total hip, femoral neck, and 1/3 radius. Patients were randomized to receive placebo (n = 125) or 60 mg denosumab (n = 127) subcutaneously every 6 months. In all subgroups, 12 or 24 months' treatment with denosumab was associated with larger BMD gains than placebo across multiple skeletal sites. Most increases were statistically significant (P < 0.05). Twice-yearly administration of denosumab, regardless of patient subgroup or skeletal site, resulted in consistent increases in BMD versus placebo at 12 and 24 months.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inhibidores de la Aromatasa/efectos adversos , Densidad Ósea/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Estrógenos , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Ligando RANK/uso terapéutico , Absorciometría de Fotón , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/complicaciones , Terapia Combinada , Denosumab , Esquema de Medicación , Femenino , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/efectos de los fármacos , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/efectos de los fármacos , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/complicaciones , Osteoporosis Posmenopáusica/inducido químicamente , Ligando RANK/administración & dosificación , Ligando RANK/antagonistas & inhibidores , Ligando RANK/inmunología , Tamoxifeno/efectos adversos , Tamoxifeno/uso terapéuticoRESUMEN
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.