316TiP - Denosumab Versus Placebo as Adjuvant Treatment for Women With Early-Stage Breast Cancer at High Risk of Disease Recurrence (D-CARE): An in Progress, Phase 3 Clinical Trial

Abstract

ABSTRACT Background Bone represents approximately 40% of all first recurrences in women with early-stage breast cancer and is a common site of distant recurrence. In preclinical studies, RANKL inhibition significantly delays skeletal tumour formation, reduces skeletal tumour burden, and prolongs survival of tumour-bearing mice. Denosumab is approved for the prevention of skeletal-related events (SREs) in patients with established bone metastases from solid tumours. Purpose The D-CARE trial is designed to assess if denosumab treatment prolongs bone metastasis-free survival (BMFS) and disease-free survival (DFS) in the adjuvant breast cancer setting. The primary endpoint of this event-driven trial is BMFS. Secondary endpoints include DFS and overall survival. Additional endpoints are safety, breast density, incidence of SREs (following the development of bone metastasis), patient reported outcomes, and biomarkers. Methods In this international, randomized, double-blind, and placebo controlled phase 3 trial, approximately 4,500 women with stage II or III breast cancer, at high risk for recurrence and with known hormone and HER-2 receptor status, are eligible. High risk is defined as biopsy evidence of breast cancer in regional lymph nodes, tumour size > 5 cm, (T3), or locally advanced disease (T4). Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination, must be planned. Patients with a prior history of breast cancer (except DCIS or LCIS) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization, or any intravenous BP use, are not eligible. Patients are randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 months, then every 3 months for a total of 5 years of treatment. Supplemental vitamin D (≥ 400 IU) and calcium (≥ 500 mg) will be administered. The trial, sponsored by Amgen Inc. and registered with the ClinicalTrials.gov identifier NCT01077154, began enrolling patients in June 2010 and is expected to complete enrolment in late 2012. Disclosure R.E. Coleman: Other substantive relationships: Expert testimony - Novartis. R. Bell: Advisory Board Member : Amgen. M. Martin: Advisory Board Member amgen, roche, bayer, novartis, gsk, sanofi. A. Braun: Employee : Amgen Inc Stock : Amgen Inc. C. Ke: Employer : Amgen Inc. Stock ownership : Amgen Inc. T. Maniar: Employee :: Amgen Inc. Stock ownership :: Amgen Inc. P.E. Goss: Honoraria for Pfizer and Novartis. All other authors have declared no conflicts of interest.