The combination of bevacizumab with chemotherapy is more beneficial in the metastatic setting rather than in the adjuvant setting for the treatment of HER2-negative breast cancer—a commentary on the E5103 randomized phase III clinical study

The randomized phase III, double-blind, clinical trial (E5103) enrolled 4,995 patients with human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer and evaluated the efficacy and the safety of humanized monoclonal antibody bevacizumab targeting vascular endothelial growth factor (VEGF) in adjuvant chemotherapeutic setting (1). The rationale of the study was based on the results from the metastatic setting where the combination of bevacizumab with chemotherapy has shown a significant improvement of progression free survival (2-7) and a pathologic complete response in the neoadjuvant setting (8-12). The E5103 aimed to improve patients’ survival outcomes. Patients were randomized in three arms: placebo with doxorubicine and cyclophosphamide followed by paclitaxel (arm A); same chemotherapeutic combination plus bevacizumab (arm B and C); in particular, patients in arm C continued bevacizumab for almost one years, together with radiation and hormonal therapy. Invasive disease-free survival (IDFS) was the primary end point. The 5-year IDFS rates were 77% (95% CI, 71% to 81%) in arm A, 76% (95% CI, 72% to 80%) in arm B, and 80% (95% CI, 77% to 83%) in arm C. The differences in IDFS between the 3 arms were not statistically significant. The overall survival (OS) at 5 years were 90% (95% CI, 87% to 92%), 86% (95% CI, 83% to 88%) and 90% (95% CI, 88% to 92%) in arms A, B and C, respectively. On the same line of the IDFS differences, the differences in OS were not statistically significant between the three groups (1)