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This article is part of the supplement: IX Madrid Breast Cancer Conference

Oral presentation

Design of RESILIENCE: a phase 3 trial comparing capecitabine in combination with sorafenib or placebo for treatment of locally advanced or metastatic HER2-negative breast cancer

J Baselga1*, F Costa2, H Gomez3, C Hudis4, B Rapoport5, H Roche6, LS Schwartzberg7, O Petrenciuc8, M Shan8 and WJ Gradishar9

  • * Corresponding author: J Baselga

Author Affiliations

1 Massachusetts General Hospital Cancer Center, Boston, MA, USA

2 Hosp Sirio Libanes, São Paulo, Brazil

3 Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru

4 Memorial Sloan-Kettering Cancer Center, New York, NY, USA

5 The Medical Oncology Centre of Rosebank, Johannesburg, South Africa

6 Institut Claudius Regaud, Toulouse, France

7 West Clinic, Memphis, TN, USA

8 Bayer HealthCare Pharmaceuticals, Toronto, ON, Canada

9 Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

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Breast Cancer Research 2011, 13(Suppl 2):O12  doi:10.1186/bcr3011


The electronic version of this article is the complete one and can be found online at: http://breast-cancer-research.com/content/13/S2/O12


Published:16 November 2011

© 2011 Baselga et al.

Introduction

A double-blind, randomized, phase 2b screening trial (SOLTI-0701) of sorafenib, an oral multikinase inhibitor, in patients with HER2-negative advanced breast cancer (BC), showed a statistically significant improvement in progression-free survival (PFS) in the sorafenib + capecitabine arm versus the placebo + capecitabine arm: 6.4 versus 4.1 months (hazard ratio = 0.58; one-sided P = 0.0006). Grade 3/4 toxicities were comparable except G3 hand-foot skin reaction/syndrome (HFSR/HFS) (44% vs. 14%). These results support a phase 3 trial of sorafenib + capecitabine in advanced BC.

Methods

RESILIENCE is an ongoing multinational, double-blind, placebo-controlled, phase 3 trial designed to assess sorafenib + capecitabine as first-line or second-line therapy in advanced HER2-negative BC (http://ClinicalTrials.gov webcite, NCT01234337). Eligibility criteria include: ≥18 years of age; ≤1 prior chemotherapy regimen for advanced BC; resistant to/failed taxane and anthracycline or no indication for further anthracycline; no prior VEGF treatment. Patients are randomized to capecitabine (1,000 mg/m2 p.o. twice daily, days 1 to 14 of 21) with sorafenib (p.o. twice daily, days 1 to 21, total dose 600 mg/day) or placebo. Sorafenib 600 mg/day corresponds to the average daily dose during SOLTI-0701 that was effective and manageable. Doses can be escalated to 2,500 mg/m2 and 800 mg/day or reduced to manage toxicity. Dose re-escalation after reduction is only allowed for sorafenib/placebo. Guidelines detail prophylactic and symptomatic therapy for HFSR/HFS. Radiographic assessment is every 6 weeks for 36 weeks, then every 9 weeks. The primary endpoint is PFS. Secondary endpoints include overall survival, time to progression, overall response rate, and duration of response. Enrollment began in November 2010 and targets ~519 patients.

Conclusion

RESILIENCE will provide definitive PFS data for sorafenib + capecitabine as first-line or second-line therapy in HER2-negative advanced BC and will better characterize the benefit-to-risk profile of this regimen.