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Breast Cancer Research and Treatment

, Volume 149, Issue 1, pp 141–149 | Cite as

Phase III study on efficacy of taxanes plus bevacizumab with or without capecitabine as first-line chemotherapy in metastatic breast cancer

  • Hans-Joachim Lück
  • Kristina Lübbe
  • Mattea Reinisch
  • Nicolai Maass
  • Gabriele Feisel-Schwickardi
  • Oliver Tomé
  • Wolfgang Janni
  • Mustafa Aydogdu
  • Tanja Neunhöffer
  • Angelika Ober
  • Bahriye Aktas
  • Tjoung-Won Park-Simon
  • Claudia Schumacher
  • Heinz-Gert Höffkes
  • Thomas Illmer
  • Harald Wagner
  • Keyur Mehta
  • Gunter von Minckwitz
  • Valentina Nekljudova
  • Sibylle LoiblEmail author
Clinical Trial

Abstract

Taxanes (T) plus bevacizumab (B) and taxanes plus capecitabine (X) showed better progression-free survival (PFS) compared to taxanes alone. Since life-threatening or highly symptomatic situations require polychemotherapy in metastatic breast cancer (MBC), combination of taxanes, capecitabine plus bevacizumab appears reasonable. TABEA (NCT01200212), a prospectively randomized, open-label, phase III trial compares taxanes (paclitaxel 80 mg/m2 i.v. d1,8,15 q22 or docetaxel 75 mg/m2 i.v. d1 q22) plus bevacizumab (15 mg/kg i.v. d1 q22) with (TBX) or without capecitabine (TB, 1800 mg/m2 daily d1–14 q22) as first-line therapy in MBC. Histologically confirmed HER2-negative, locally advanced or MBC patients with a chemotherapy indication and measurable or non-measurable target lesions (RECIST criteria) were included. Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (complete response, partial response, stable disease ≥24 weeks), 3-year overall survival, PFS in patients ≥65 years, toxicity, and compliance. We assumed 10 and 13.3 months PFS for TB and TBX, respectively (HR = 0.75), requiring 432 patients and 386 events. Preplanned interim futility and safety analyses after 100 events in 202 patients showed no efficacy benefit and higher toxicity for TBX. Recruitment and therapy were stopped following advice from the IDMC. Final analysis revealed a HR 1.13 [95 %CI 0.806–1.59], P = 0.474, for PFS. Overall grade 3–4 adverse event (77.3 vs. 62.1 %, P = 0.014) and serious adverse event (40.0 vs. 30.2 %, P = 0.127) rates were higher for TBX after 26.1 months median follow-up, with six deaths for TBX versus 1 for TB. Adding capecitabine to TB cannot be recommended as first-line therapy in MBC.

Keywords

Metastatic breast cancer Capecitabine Bevacizumab Taxane Response Progression-free survival 

Notes

Acknowledgments

This work was supported by Roche Germany. The funders had no access to the study database and were not involved in the analysis and interpretation of the results. No grant number applicable.

Conflict of interest

All other authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Hans-Joachim Lück
    • 1
  • Kristina Lübbe
    • 2
  • Mattea Reinisch
    • 3
  • Nicolai Maass
    • 4
  • Gabriele Feisel-Schwickardi
    • 5
  • Oliver Tomé
    • 6
  • Wolfgang Janni
    • 7
  • Mustafa Aydogdu
    • 8
  • Tanja Neunhöffer
    • 9
  • Angelika Ober
    • 10
  • Bahriye Aktas
    • 11
  • Tjoung-Won Park-Simon
    • 12
  • Claudia Schumacher
    • 13
  • Heinz-Gert Höffkes
    • 14
  • Thomas Illmer
    • 15
  • Harald Wagner
    • 16
  • Keyur Mehta
    • 3
  • Gunter von Minckwitz
    • 3
  • Valentina Nekljudova
    • 3
  • Sibylle Loibl
    • 3
    Email author
  1. 1.Gynecologic Oncology Practice HannoverHannoverGermany
  2. 2.Breast CentreHenriettenstiftung HannoverHannoverGermany
  3. 3.German Breast GroupNeu-IsenburgGermany
  4. 4.Department Obstetrics and GynecologyUniversity Women’s ClinicAachenGermany
  5. 5.Department Obstetrics and GynecologyKlinikum KasselKasselGermany
  6. 6.Breast CenterSt. Vincentius Clinic KarlsruheKarlsruheGermany
  7. 7.Department Obstetrics and GynecologyUniversity Hospital UlmUlmGermany
  8. 8.Breast CenterKlinikum Bremen MitteBremenGermany
  9. 9.Breast CenterDr.-Horst-Schmidt-KlinikenWiesbadenGermany
  10. 10.Breast CenterSt. Vincenz Hospital LimburgLimburg an der LahnGermany
  11. 11.Department Obstetrics and GynecologyUniversity Hospital EssenEssenGermany
  12. 12.Department Obstetrics and GynecologyHannover Medical SchoolHannoverGermany
  13. 13.Breast CenterSt. Elisabeth Hospital Köln-HohenlindKölnGermany
  14. 14.Breast CenterKlinikum FuldaFuldaGermany
  15. 15.Practice for Internal Medicine and Hematology DresdenDresdenGermany
  16. 16.Oncological Clinic Drs. med. Wilke/WagnerFürthGermany

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