Bone Health Outcomes from the International, Multicenter, Randomized, Phase 3, Placebo-Controlled D-CARE Study Assessing Adjuvant Denosumab in Early Breast Cancer

• Published in: Advances in therapy 2021-08, Vol.38 (8), p.4569-4580
• Main Authors: Coleman, Robert, Zhou, Ying, Jandial, Danielle, Cadieux, Benoit, Chan, Arlene
• Format: Article
• Language: English
• Subjects: Bone Neoplasms - drug therapy; Breast Neoplasms - drug therapy; Brief Report; Cardiology; Denosumab - therapeutic use; Double-Blind Method; Endocrinology; Female; Humans; Internal Medicine; Medicine; Medicine & Public Health; Middle Aged; NCT; NCT01077154; Neoplasm Recurrence, Local; Oncology; Outcome Assessment, Health Care; Pharmacology/Toxicology; Rheumatology
• ISSN: 0741-238X; 1865-8652
• DOI: 10.1007/s12325-021-01812-9

Introduction D-CARE, an international, phase 3, randomized, double-blind, placebo-controlled study in women with early-stage breast cancer at high risk of disease recurrence, failed to meet its primary endpoint—improvement in bone metastasis-free survival (BMFS) with adjuvant denosumab vs placebo injections. As a result of the limitations of assessing BMFS, which includes relapse in bone with and without extraskeletal recurrences and deaths from any cause, the prespecified exploratory bone endpoints’ analysis may provide a more clinically meaningful effect of denosumab in this disease setting. Methods The study enrolled women (aged ≥ 18 years) with histologically confirmed stage II/III breast cancer. Patients treated with adjuvant/neoadjuvant chemotherapy meeting inclusion criteria were randomly assigned 1:1 to receive either denosumab (120 mg) or placebo subcutaneously every 3–4 weeks for about 6 months and then every 3 months for a total treatment duration of 5 years. Five prespecified exploratory bone endpoints and post hoc subgroup analysis based on age (