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Effect of Once-Weekly Epoetin Beta on Survival in Patients With Metastatic Breast Cancer Receiving Anthracycline- and/or Taxane-Based Chemotherapy: Results of the Breast Cancer—Anemia and the Value of Erythropoietin (BRAVE) Study

Matti Aapro, Robert C. Leonard, Agustí Barnadas, Maurizio Marangolo, Michael Untch, Nikolaos Malamos, José Mayordomo, Dietmar Reichert, José Luiz Pedrini, Lidia Ukarma, Armin Scherhag, Hans-Ulrich Burger

From the Institut Multidisciplinaire d'Oncologie, Clinique de Genolier, Genolier; F. Hoffmann–La Roche Ltd, Basel, Switzerland; Cancer Services and Clinical Haematology, Imperial College, Charing Cross Hospital, London, United Kingdom; Hospital de Sant Pau, Barcelona; Hospital Clinico Universitario de Zaragoza, Zaragoza, Spain; Divisione Oncologia, Ospedale Provinciale Sta Maria delle Croci, Ravenna, Italy; Helios Klinikum, Berlin Buch; Medical Clinic, University Hospital Mannheim, University of Heidelberg, Heidelberg; Staedtische Kliniken Oldenburg, Oldenburg, Germany; Elena Venizelou Hospital, Athens, Greece; and Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil

Corresponding author: Matti Aapro, Institut Multidisciplinaire d'Oncologie, Clinique de Genolier, 1 route du Muids, Genolier, Switzerland 1272; e-mail: maapro{at}genolier.net

Purpose The Breast Cancer—Anemia and the Value of Erythropoietin (BRAVE) study evaluated whether epoetin beta would improve survival in patients with metastatic breast cancer (MBC).

Patients and Methods BRAVE was an open-label, randomized, multicenter study in patients with MBC treated with anthracycline- and/or taxane-based chemotherapy. Patients (hemoglobin [Hb] < 12.9 g/dL) were randomly assigned (1:1) to epoetin beta 30,000 U subcutaneously once weekly or control for 24 weeks. The primary efficacy variable was overall survival. Secondary efficacy outcomes included progression-free survival, transfusion- and severe anemia–free survival, Hb response, safety, and quality of life (QoL).

Results After 18 months of follow-up, 62 (27%) of 231 patients survived with epoetin beta therapy and 63 (27%) of 232 with control. No difference was detected in overall survival (hazard ratio [HR] = 1.07; 95% CI, 0.87 to 1.33, P = .522) or progression-free survival (HR = 1.07; 95% CI, 0.89 to 1.30, P = .448). There was a statistically significant benefit on transfusion- and severe anemia–free survival compared with control (HR = 0.59; P = .0097). Median Hb level increased with epoetin beta (11.7 g/dL at baseline to 13.3 g/dL at 24 weeks) but did not change with control (11.5 v 11.4 g/dL). Patients receiving epoetin beta experienced more thromboembolic events (TEEs) compared with controls (13% v 6%; P = .012) with no difference in serious TEEs (4% v 3%). Epoetin beta did not significantly improve QoL in this study where patients had a high baseline Hb value.

Conclusion In patients with MBC receiving chemotherapy and initial Hb less than 12.9 g/dL, epoetin beta increased Hb. No difference was detected in overall survival. Because of its superiority design, this study cannot, however, exclude clinically important differences in survival with absolute certainty.

Supported by F. Hoffmann–La Roche Ltd, Basel, Switzerland.

Presented as a poster at the 29th Annual San Antonio Breast Cancer Symposium, December 14-17, 2006, San Antonio, TX.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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Related Correspondence

• Effect of Epoetin on Survival in Patients With Breast Cancer
  Giovanni Codacci-Pisanelli, Gian Paolo Spinelli, and Silverio Tomao
  JCO 2008 26: 2599 [Full Text]

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