Abstract OT1-04-04: A phase 2 randomized, double-blind, placebo-controlled trial of endocrine therapy ± radium-223 dichloride in HER2-negative, hormone receptor–positive breast cancer patients with bone metastases
Authors: Coleman RE , Fried G , Petrenciuc O , Sawhney A , Li R , Rugo HS 
Published: March 2017

Abstract
Background: Bone-metastatic breast cancer (MBC) treatment is limited. In a phase 2a study of bone-dominant MBC patients, radium-223, a first-in-class α emitter with targeted cytotoxic effect on bone metastases (mets), reduced bone biomarker levels with favorable safety (Coleman et al. Breast Cancer Res Treat. 2014).
Trial design: This study evaluates efficacy and safety of radium-223 versus placebo (pbo), each + endocrine treatment (ET), in patients with HER2- estrogen receptor+ (ER+)bone-dominant MBC (NCT02258464). Patients receive (1:1) radium-223 50 kBq/kg IV or pbo q 4 wk (6 cycles) + ET + denosumab or bisphosphonates + best supportive care. Stratification is by geographic region (EU/N America vs Asia), number of prior ET lines (1 vs ≥ 2) for MBC, and number of prior skeletal-related events (SREs) (1 vs 2).
Eligibility criteria: Eligible patients are pre- or postmenopausal with HER2- ER+ bone-dominant MBC and ≥ 2 bone mets or with soft tissue and/or visceral mets, and 1-2 prior SREs (external beam radiotherapy, pathologic bone fracture, spinal cord compression, orthopedic surgery); they have received ≥ 1 line of ET for MBC and are considered appropriate for further ET. Patients must have evaluable disease (RECIST 1.1), be taking bisphosphonates or denosumab for ≥ 1 month before study treatment, have an ECOG score 0-1, and have adequate hematologic, renal, and liver function. Patients must not have had visceral or brain mets or leptomeningeal disease, or need chemotherapy for MBC, and must not be suitable for everolimus for MBC. Patients are not eligible if they had prior radium-223 treatment or have untreated spinal cord compression.
Specific aims: The primary end point is SSE-free survival (SSE-FS). Secondary end points are radiologic progression-free survival; overall survival; times to opioid use, pain progression, and cytotoxic chemotherapy; pain improvement rate; and safety. Patients are assessed for efficacy and safety and are followed to SSE, radiologic progression, death, or withdrawal.
Statistical methods: Assuming 1-sided α 0.1, power 90%, ∼ 119 SSE-FS events are needed for analysis. Time-to-event analysis will use a log-rank test, accounting for stratification. Kaplan-Meier estimates and survival curves will be given for each treatment group. Safety analyses will be descriptive.
Present and target accrual: Target accrual is ∼ 227. Currently, 40 patients are randomized.
Contact Oana Petrenciuc, Bayer HealthCare Pharmaceuticals, oana.petrenciuc@bayer.com, for more information.
Citation Format: Coleman RE, Fried G, Petrenciuc O, Sawhney A, Li R, Rugo HS. A phase 2 randomized, double-blind, placebo-controlled trial of endocrine therapy ± radium-223 dichloride in HER2-negative, hormone receptor–positive breast cancer patients with bone metastases [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-04-04.