Research in context
Evidence before this study
This protocol was undertaken starting in 2007, before which, all relevant data from trials of adding gemcitabine, capecitabine, and bevavicizumab to chemotherapy in the metastatic, adjuvant, and neoadjuvant settings for breast cancer were reviewed using the PubMed database, personal files, and meeting presentations. However, no specific records of literature reviews were kept during the time this trial was developed during 2005–06. As noted in detail in our previous publication on the proportion of patients achieving a response, the decision to test capecitabine and gemcitabine was based on previous reports that these compounds added to taxane-based chemotherapy increased progression-free survival in patients with metastatic breast cancer. Likewise, previous trials had shown that bevacizumab added to chemotherapy increased response rates and progression-free survival in patients with advanced breast cancer. The potential benefit of addition of bevacizumab to treatment of breast cancer has also been reviewed not only by us but also by others. The previous results suggested that adding each of these compounds to chemotherapy in either adjuvant or neoadjuvant settings would increase the benefits in terms of response and patient outcomes. Those data are summarised in this paper and in the paper showing the proportion of patients achieving a response, published in 2012.
Added value of this study
The results reported here agree with the final results of neoadjuvant and adjuvant trials, which have shown that neither gemcitabine nor capecitabine improves on the efficacy of chemotherapy for early stage breast cancer. The results reported here on the effect of adding neoadjuvant and adjuvant bevacizumab, on the other hand, contradict other reports in which addition of either adjuvant or neoadjuvant bevacizumab to chemotherapy for breast cancer did not significantly improve the proportion of patients achieving a response or patient outcomes. We noted a significant increase in pathological complete response as well as disease-free survival and overall survival with bevacizumab given with neoadjuvant chemotherapy and continued postoperatively. We also noted a preferential effect in hormone-receptor-positive breast cancer, whereas others have suggested a greater benefit for triple-negative breast cancer. However, this is the only study in which bevacizumab was added to neoadjuvant chemotherapy and added to postoperative adjuvant therapy.
Implications of all the available evidence
Although it would be premature to apply the results of B-40 reported here to routine practice, there are biologically plausible explanations for the results reported here, despite the contradictory results from other trials. Based on these results in the context of other studies, we cannot recommend routine use of bevacizumab for neoadjuvant or adjuvant treatment of operable breast cancer. However, with the correlative science studies that will be done with the tumour tissue and blood collected in advance from the patients in this trial, a more refined selection of patients who might benefit most from adding bevacizumab might be possible. Moreover, additional trials could be appropriate to clarify and refine these results to obtain more actionable information about the use of bevacizumab in this setting, with possible emphasis on patients who do not achieve a pathological complete response with neoadjuvant chemotherapy plus bevacizumab.