Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer

Abstract

Background-Bevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer. The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide, would increase the rates of pathological complete response in the breast in women with operable, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response.

The Longitudinal Transcriptional Response to Neoadjuvant Chemotherapy with and without Bevacizumab in Breast Cancer

“…More patients achieved pCR in the combination-therapy arm compared to the chemotherapy alone arm, in line with reports from previous studies (6,7,10,11). A significant benefit of adding bevacizumab was observed in the ER-positive subgroup consistent with the larger NSAPB-B40 trial (11), in contradiction to the GeparQuinto trial, where the ERnegative tumors were found to benefit from bevacizumab (10), and the CALGB40603 study, including patients with a low ER expression, or triple negative tumors (6). The clinical toxicity increased with bevacizumab treatment, as more patients experienced febrile neutropenia in addition to hypertension and episodes of bleeding.…”

“…Increases in febrile neutropenia and hypertension have also been seen in similar studies (10,11). The clinical practice guidelines at the time of the study were not recommending the use of G-CSF for all patients, only those having experienced febrile neutropenia, and this may have increased the frequency of this adverse event.…”

“…Blocking VEGF by bevacizumab, a monoclonal antibody, has been proposed to cause inhibition of neovascularization, regression of existing immature micro-vessels, and normalization of abnormal vasculature (4,5); this has consequences for the flux of oxygen, nutrients, metabolites and therapeutic agents, ultimately preventing tumor growth and resulting in tumor shrinkage. However, addition of bevacizumab to standard chemotherapy in unselected breast cancer patients has resulted only in a modest increase in response rate and progression free survival (6)(7)(8)(9)(10)(11).…”

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial

“…G-CSF support was used in 93 % of chemotherapy cycles resulting in low rates of neutropenia (3 %). In contrast, the NSABP-B40 trial [26] reported that in the neoadjuvant docetaxel and gemcitabine arm the toxic effect with the greatest increase in frequency compared with the toxic effects of docetaxel alone was neutropenia in 34 % of the patients (NCI grade 3 and 4). Trials in the metastatic setting report increased rates of neutropenia (47.9 %) and thrombocytopenia (6.1 %) compared with our results.…”

Chemotherapy and Mechanisms of Resistance in Breast Cancer

“…Neoadjuvant chemotherapy is defined as a treatment option where chemotherapy is introduced before local treatment, either surgery or radiotherapy (Bear, 1998). This was introduced by De Lena et al (1978) who administered adriablastin and vincristine in 110 women with advanced BC, achieving response rates of 70% partial.…”