Breast Cancer Research and Treatment

, Volume 122, Issue 2, pp 409–418 | Cite as

Analysis of overall survival from a phase III study of ixabepilone plus capecitabine versus capecitabine in patients with MBC resistant to anthracyclines and taxanes

  • Gabriel N. Hortobagyi
  • Henry L. Gomez
  • Rubi K. Li
  • Hyun-Cheol Chung
  • Luis E. Fein
  • Valorie F. Chan
  • Jacek Jassem
  • Guillermo L. Lerzo
  • Xavier B. Pivot
  • Fernando Hurtado de Mendoza
  • Binghe Xu
  • Linda T. Vahdat
  • Ronald A. Peck
  • Pralay Mukhopadhyay
  • Henri H. Roché
Clinical trial

Abstract

Limited proven treatment options exist for patients with metastatic breast cancer (MBC) resistant to anthracycline and taxane treatment. Ixabepilone, a novel semisynthetic analog of epothilone B, has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes. In combination with capecitabine in a phase III trial (CA163-046) in this setting, ixabepilone prolonged progression-free survival and increased objective response rate relative to capecitabine (Thomas et al. J Clin Oncol 25:5210–5217, 2007). Here, we report the results of overall survival (OS), a secondary efficacy endpoint from the CA163-046 trial. Seven hundred fifty-two patients with MBC resistant to anthracyclines and taxanes were randomized to ixabepilone (40 mg/m2 intravenously on day 1 of a 21-day cycle) plus capecitabine (2,000 mg/m2 orally on days 1 through 14 of a 21-day cycle) or capecitabine alone (2,500 mg/m2 on the same schedule). Patients receiving ixabepilone plus capecitabine treatment had a median survival of 12.9 months compared to 11.1 months for patients receiving capecitabine alone (HR = 0.9; 95%CI: 077–1.05; P = 0.19). This observed increase in median OS favored the combination; however, the difference was not statistically significant. Predefined subset analyses showed a clinically meaningful increase in OS in KPS 70–80 patients receiving ixabepilone plus capecitabine (HR = 0.75; 95% CI: 0.58–0.98). Ixabepilone plus capecitabine did not show a significant improvement in survival compared to capecitabine alone in patients with MBC resistant to anthracyclines and taxanes. The observed differences in survival favored the combination arm. A clinical benefit was also seen in patients in the KPS 70–80 subgroup (ClinicalTrials.gov number, NCT000080301).

Keywords

Epothilone Ixabepilone Metastatic breast cancer Overall survival 

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Gabriel N. Hortobagyi
    • 1
  • Henry L. Gomez
    • 2
  • Rubi K. Li
    • 3
  • Hyun-Cheol Chung
    • 4
  • Luis E. Fein
    • 5
  • Valorie F. Chan
    • 6
  • Jacek Jassem
    • 7
  • Guillermo L. Lerzo
    • 8
  • Xavier B. Pivot
    • 9
  • Fernando Hurtado de Mendoza
    • 10
  • Binghe Xu
    • 11
  • Linda T. Vahdat
    • 12
  • Ronald A. Peck
    • 13
  • Pralay Mukhopadhyay
    • 13
  • Henri H. Roché
    • 14
  1. 1.Department of Breast Medical OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.The Instituto Nacional de Enfermedades NeoplasicasLimaPeru
  3. 3.The St. Luke’s Medical CenterQuezon CityPhilippines
  4. 4.The Yonsei Cancer CenterSeoulRepublic of Korea
  5. 5.The Centro de Oncologia RosarioSanta FeArgentina
  6. 6.The Veterans Memorial Medical CenterQuezon CityPhilippines
  7. 7.The Medical University of GdanskGdanskPoland
  8. 8.The Hospital de Oncologia ‘Maria Curie’Buenos AiresArgentina
  9. 9.University Hospital of BesançonInsermFrance
  10. 10.The Hospital Nacional Edgardo Rebagliati MartinsLimaPeru
  11. 11.The Cancer Hospital—Chinese Academy of Medical SciencesBeijingChina
  12. 12.The Weill Medical College of Cornell UniversityNew YorkUSA
  13. 13.Research and DevelopmentBristol-Myers SquibbWallingfordUSA
  14. 14.The Institut Claudius RegaudToulouseFrance

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