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Poster display

2901 - A phase 2 randomized, double-blind, placebo-controlled trial of radium-223 dichloride with exemestane and everolimus in patients with HER2–negative hormone receptor–positive breast cancer and bone metastases


10 Oct 2016


Poster display


Hope Rugo


Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365


H. Rugo1, O. Petrenciuc2, A. Zhang3, R. Li4, R.E. Coleman5

Author affiliations

  • 1 Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 2 Global Clinical Development, Pharmaceuticals Division of Bayer, Whippany/US
  • 3 Global Development, Pharmaceuticals Division of Bayer, Whippany/US
  • 4 Global Research And Development Statistics, Pharmaceuticals Division of Bayer, Whippany/US
  • 5 Oncology, University of Sheffield, Weston Park Hospital, S10 2SJ - Sheffield/GB


Abstract 2901


Treatment options for bone-dominant metastatic breast cancer (MBC) are limited. Radium-223 (Ra-223), a first-in-class α emitter with a targeted antitumor effect on bone metastases (mets), was well tolerated and reduced bone biomarker levels in a phase 2 study in patients with bone-dominant MBC (Coleman et al. Breast Cancer Res Treat 2014). In patients with HER2 estrogen receptor+ (ER+) bone-dominant MBC, everolimus + exemestane (EVE + EXE) improved progression-free survival (PFS) versus EXE alone. Ra-223 plus EVE + EXE may improve outcomes in patients with HER2 ER+ bone-dominant MBC; this trial will evaluate efficacy and safety of Ra-223 versus placebo in these patients (NCT02258451).

Trial design

Eligible patients are pre- or postmenopausal with HER2 ER+ MBC and ≥ 2 bone or soft tissue mets. Patients must have measurable disease per RECIST v1.1, ≥ 1 prior line of hormone therapy for MBC, and 1-2 prior skeletal-related events; be on bisphosphonates or denosumab; and have an ECOG score of 0-1. Patients must have had no past or current need for chemotherapy for MBC, no unresolved spinal cord compression, and no prior EVE treatment. Patients are randomized to receive (1:1) Ra-223 (50 kBq/kg [55 kBq/kg after National Institute of Standards and Technology update] IV) or placebo × 6 cycles q 4 wk plus EXE (25 mg PO q d) + EVE (10 mg PO q d) plus best supportive care. EXE + EVE continues until disease progression or unacceptable toxicity. Stratification is by geographic region (EU/N Amer vs Asia), prior hormone therapy (1 vs ≥ 2), and presence of visceral disease (yes vs no). Safety and efficacy are assessed every 4 weeks. Long-term safety is assessed until study termination. The primary end point is symptomatic skeletal event–free survival (SSE-FS). Secondary end points are overall survival; times to opiate use, pain progression, and chemotherapy; radiologic PFS; and safety. Assuming a 1-sided α of 0.1, 90% power, ∼ 160 SSE-FS events will be required for the analysis. Efficacy will be analyzed by a stratified log-rank test. Safety analysis will be descriptive. Estimated enrollment is ∼ 311 patients. Currently, 72 patients are randomized.

Clinical trial identification


Legal entity responsible for the study

Pharmaceuticals Division of Bayer


Pharmaceuticals Division of Bayer


H. Rugo: Speakers bureau, honoraria: Genomic Health; research funding: Plexxikon, Macrogenics, OBI, Eisai, Pfizer, Novartis, Lilly, GlaxoSmithKline, Genentech, Celsion, Nektar, Merck; travel, accommodations, expenses: Novartis, Nektar, Roche/Genentech, OBI, Mylan. O. Petrenciuc: Employed by and travel, accommodations, expenses from Bayer. A. Zhang, R. Li: Employed by Bayer. R.E. Coleman: Expert testimony for Novartis; research funding from Bayer.

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