title: 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.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut Multidisciplinaire d'Oncologie, Clinique de Genolier, 1 route du Muids, Genolier, Switzerland. maapro@genolier.net
authors.forename: Matti
authors.initials: M
authors.lastname: Aapro
authors.forename: Robert C
authors.initials: RC
authors.lastname: Leonard
authors.forename: Agustí
authors.initials: A
authors.lastname: Barnadas
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marangolo
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Malamos
authors.forename: José
authors.initials: J
authors.lastname: Mayordomo
authors.forename: Dietmar
authors.initials: D
authors.lastname: Reichert
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Pedrini
authors.forename: Lidia
authors.initials: L
authors.lastname: Ukarma
authors.forename: Armin
authors.initials: A
authors.lastname: Scherhag
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Burger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced / Q000517:prevention & control*; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007279:Injections, Subcutaneous; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011788:Quality of Life; D011994:Recombinant Proteins; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D006454:Hemoglobins; D011994:Recombinant Proteins; D043823:Taxoids; C103998:epoetin beta; D004921:Erythropoietin