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

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.