Final overall survival results and effect of prolonged (≥1 year) first-line bevacizumab-containing therapy for metastatic breast cancer in the ATHENA trial

  • Ian SmithEmail author
  • Jean-Yves Pierga
  • Laura Biganzoli
  • Hernan Cortes-Funes
  • Christoph Thomssen
  • Silvana Saracchini
  • Bella Nisenbaum
  • Ignacio Pelaez
  • Anja-Alexandra Duenne
  • Kathleen I. Pritchard
Clinical Trial


The ATHENA study expanded on the safety and efficacy data derived from first-line trials of bevacizumab combined with standard chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC). In ATHENA, 2,264 patients received first-line bevacizumab-containing therapy in routine oncology practice. Overall survival (OS) data are now mature; additional analyses from this large data set can provide insights into treatment duration and the effect of prolonged bevacizumab exposure, where data are currently limited. Patients with HER2-negative LR/mBC received first-line bevacizumab with standard chemotherapy until disease progression, unacceptable toxicity, or physician/patient decision. We performed subgroup analyses on data from patients treated for ≥12 months and those who continued single-agent bevacizumab after stopping chemotherapy. After median follow-up of 20.1 months, median OS was 25.2 months (95% confidence interval [CI] 24.0–26.3 months) in the entire population. Median OS was 30.0 months (95% CI 28.5–32.7 months) in 1,205 patients who continued bevacizumab after discontinuation of chemotherapy and 18.4 months (95% CI 17.2–19.7 months) in 1,058 patients who discontinued bevacizumab before or at the same time as stopping chemotherapy. Bevacizumab treatment was continued for ≥12 months in 473 patients (21%). In most, bevacizumab was administered as monotherapy for extended periods after stopping chemotherapy. In the subgroup of patients treated for ≥12 months, the median time to onset of grade 3–5 adverse events was 5.0 months. There was no evidence that first onset of adverse events of special interest, except for proteinuria, was more common in later than earlier cycles. No relationship was detected between development of hypertension and OS. Findings from these analyses suggest that patients with LR/mBC can receive bevacizumab for prolonged periods without major toxicity or progression of disease. In the absence of progression, continuation of single-agent bevacizumab appears to be a reasonable approach, with minimal toxicity and the possibility of long-term disease control.


Angiogenesis Bevacizumab Duration First-line therapy Maintenance Metastatic breast cancer 



The ATHENA study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party statistical analysis and medical writing for this manuscript was provided by F. Hoffmann-La Roche Ltd, but the development, review, and final approval of the manuscript remained the responsibility of the authors.

Conflict of interest

Ian Smith has received honoraria for lecturing from Roche. Jean-Yves Pierga has a consultant/advisory role with and has received funding from Roche and Genentech. Laura Biganzoli has a consultant/advisory role with Roche. Christoph Thomssen has received remuneration from Roche and Sanofi-Aventis. Anja-Alexandra Duenne is an employee of F. Hoffmann-La Roche Ltd. Kathleen I Prichard has a consultant/advisory role with Abraxis, Pfizer, Novartis, Boehringer-Ingelheim, Roche, and GlaxoSmithKline. The other authors have no conflict of interest to declare.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Ian Smith
    • 1
    • 2
    Email author
  • Jean-Yves Pierga
    • 3
  • Laura Biganzoli
    • 4
  • Hernan Cortes-Funes
    • 5
  • Christoph Thomssen
    • 6
  • Silvana Saracchini
    • 7
  • Bella Nisenbaum
    • 8
  • Ignacio Pelaez
    • 9
  • Anja-Alexandra Duenne
    • 10
  • Kathleen I. Pritchard
    • 11
  1. 1.Breast UnitRoyal Marsden HospitalLondonUK
  2. 2.The Institute of Cancer ResearchLondonUK
  3. 3.Department of Medical OncologyInstitut Curie, Université Paris DescartesParisFrance
  4. 4.Medical Oncology Unit, Department of OncologyPrato Hospital, Tuscany Cancer InstitutePratoItaly
  5. 5.Oncology DepartmentHospital Universitario 12 de OctubreMadridSpain
  6. 6.Department of GynaecologyMartin-Luther-Universität Halle-WittenbergHalleGermany
  7. 7.Santa Maria Degli AngeliPordenoneItaly
  8. 8.Meir HospitalKfar SabaIsrael
  9. 9.Hospital de CabueñesGijonSpain
  10. 10.F. Hoffmann-La Roche LtdBaselSwitzerland
  11. 11.Sunnybrook Odette Cancer Centre and Department of MedicineUniversity of TorontoTorontoCanada

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