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Volume 13 Supplement 2

IX Madrid Breast Cancer Conference

  • Oral presentation
  • Open Access

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
Breast Cancer Research201113(Suppl 2):O12

https://doi.org/10.1186/bcr3011

Published: 16 November 2011

Keywords

Breast CancerBreast CancerSorafenibCapecitabineTaxane

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, 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.

Authors’ Affiliations

(1)
Massachusetts General Hospital Cancer Center, Boston, USA
(2)
Hosp Sirio Libanes, São Paulo, Brazil
(3)
Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru
(4)
Memorial Sloan-Kettering Cancer Center, New York, USA
(5)
The Medical Oncology Centre of Rosebank, Johannesburg, South Africa
(6)
Institut Claudius Regaud, Toulouse, France
(7)
West Clinic, Memphis, USA
(8)
Bayer HealthCare Pharmaceuticals, Toronto, Canada
(9)
Feinberg School of Medicine, Northwestern University, Chicago, USA

Copyright

© Baselga et al. 2011

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