Adjuvant bevacizumab does not improve invasive disease-free survival in triple-negative breast cancer
Patients who received one year of bevacizumab in addition to chemotherapy for the postsurgical treatment of triple-negative breast cancer (TNBC) have no statistically significant improvement in invasive disease-free survival compared with patients treated with chemotherapy alone, according to the primary results of the phase III BEATRICE study.
Prior research showed that bevacizumab combined with chemotherapy significantly improves progression-free survival (PFS) in metastatic breast cancer and improves pathologic complete response (pCR) in the neoadjuvant setting. The dependence of micrometastases on angiogenesis formed the rationale to test whether patients might benefit from anti-angiogenic strategies, such as bevacizumab, applied in the adjuvant setting. In BEATRICE, an open-label, multinational, phase III study, researchers randomly assigned 2,591 patients with operable, centrally-confirmed triple-negative primary invasive breast cancer to four or more cycles of anthracycline- or taxane-based chemotherapy with or without one year of bevacizumab. The primary objective of BEATRICE was to compare invasive disease-free survival (IDFS) with adjuvant chemotherapy with or without 1 year of bevacizumab. Secondary outcome measures included overall survival (OS), breast cancer-free interval, disease-free survival (DFS), distant DFS, and safety.
At a median follow-up of 32 months, the hazard ratio for IDFS was 0.87 (95% CI 0.72–1.07) in favor of patients assigned to chemotherapy and bevacizumab (3 year IDFS 82,7% with chemotherapy alone vs. 83,7% with chemotherapy plus bevacizumab). Researchers reported 107 deaths among patients who received chemotherapy alone compared with 93 deaths among those who received chemotherapy and bevacizumab. No difference was found in the amount of chemotherapy delivered and no increase in the risk for fatal adverse events in patients assigned to bevacizumab was reported. However, the addition of bevacizumab to chemotherapy was associated with an increase in grade 3 or worse hypertension, left ventricular dysfunction and congestive heart failure.
In summary, there was no statistically significant improvement in IDFS with the addition of 1 year of bevacizumab to adjuvant chemotherapy for TNBC. Further follow-up is required to assess the impact of BEV on OS. The safety profile was consistent with previous reports in metastatic breast cancer with a low incidence of fatal adverse events. As such, this study did not confirm the hypothesis that adding bevacizumab to chemotherapy would improve patients’ outcomes and, sadly for patients, nothing extra can be added to chemotherapy for early TNBC.
D. Cameron, J. Brown, R. Dent et al. Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple-negative breast cancer. Presented at SABCS 2012; Abstract S6-5.