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.
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.
Aapro
Matti
M
Institut Multidisciplinaire d'Oncologie, Clinique de Genolier, 1 route du Muids, Genolier, Switzerland. maapro@genolier.net
Leonard
Robert C
RC
Barnadas
Agustí
A
Marangolo
Maurizio
M
Untch
Michael
M
Malamos
Nikolaos
N
Mayordomo
José
J
Reichert
Dietmar
D
Pedrini
José Luiz
JL
Ukarma
Lidia
L
Scherhag
Armin
A
Burger
Hans-Ulrich
HU
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
D018943:Anthracyclines; D006454:Hemoglobins; D011994:Recombinant Proteins; D043823:Taxoids; C103998:epoetin beta; D004921:Erythropoietin