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

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Breast Unit, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK

    Ian Smith

  2. The Institute of Cancer Research, London, UK

    Ian Smith

  3. Department of Medical Oncology, Institut Curie, Université Paris Descartes, Paris, France

    Jean-Yves Pierga

  4. Medical Oncology Unit, Department of Oncology, Prato Hospital, Tuscany Cancer Institute, Prato, Italy

    Laura Biganzoli

  5. Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    Hernan Cortes-Funes

  6. Department of Gynaecology, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany

    Christoph Thomssen

  7. Santa Maria Degli Angeli, Pordenone, Italy

    Silvana Saracchini

  8. Meir Hospital, Kfar Saba, Israel

    Bella Nisenbaum

  9. Hospital de Cabueñes, Gijon, Spain

    Ignacio Pelaez

  10. F. Hoffmann-La Roche Ltd, Basel, Switzerland

    Anja-Alexandra Duenne

  11. Sunnybrook Odette Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada

    Kathleen I. Pritchard

Authors
  1. Ian Smith
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  2. Jean-Yves Pierga
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  3. Laura Biganzoli
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  7. Bella Nisenbaum
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  9. Anja-Alexandra Duenne
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  10. Kathleen I. Pritchard
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Correspondence to Ian Smith.

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Smith, I., Pierga, JY., Biganzoli, L. et al. Final overall survival results and effect of prolonged (≥1 year) first-line bevacizumab-containing therapy for metastatic breast cancer in the ATHENA trial. Breast Cancer Res Treat 130, 133–143 (2011). https://doi.org/10.1007/s10549-011-1695-8

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  • DOI: https://doi.org/10.1007/s10549-011-1695-8

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