Neoadjuvant Bevacizumab plus Chemotherapy versus Chemotherapy Alone to Treat Non-Metastatic Breast Cancer: A Meta-Analysis of Randomised Controlled Trials

Abstract

PurposeResults from previous randomised controlled trials (RCTs) investigating whether the addition of bevacizumab to neoadjuvant chemotherapy (NAC) could statistically significantly increase the pathological complete response (pCR) and to identify which subgroup would benefit most from such regimens have produced conflicting results. This meta-analysis was designed to assess the efficacy and safety of bevacizumab plus chemotherapy compared with chemotherapy alone in the neoadjuvant setting.MethodsA literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane library was performed to identify eligible studies. The primary endpoint of interest was pCR. The secondary endpoints were clinical complete rate (cCR), surgery rate, breast-conserving surgery (BCS) rate, and toxicity. The meta-analysis was performed using Review Manager software version 5.3.ResultsNine RCTs matched the selection criteria, yielding a total of 4967 patients (bevacizumab plus chemotherapy: 50.1%, chemotherapy alone: 49.9%). The results of this meta-analysis demonstrated that the addition of bevacizumab to NAC significantly increased the pCR rate (odds ratio [OR] = 1.34 [1.18–1.54]; P < 0.0001) compared with chemotherapy alone. Subgroup analysis showed that the effect of bevacizumab was more pronounced in patients with HER2-negative cancer (OR = 1.34 [1.17–1.54]; P < 0.0001) compared with HER2-positive cancer (OR = 1.69 [0.90–3.20]; P = 0.11). Similarly, in patients with HER2-negative cancer, the effect of bevacizumab was also more pronounced in patients with HR-negative cancer (OR = 1.38 [1.09–1.74]; P = 0.007) compared with HR-positive cancer (OR = 1.36 [0.78–2.35]; P = 0.27). No significant differences were observed between the groups with respect to cCR, surgery rate, or BCS rate. Additionally bevacizumab was associated with a higher incidence of neutropenia, febrile neutropenia, and hand–foot syndrome.ConclusionsHigher proportions of patients achieved pCR when bevacizumab was added to NAC compared with when they received chemotherapy alone; acceptable toxicities were also found. Subgroup analysis demonstrated that patients with histologically confirmed HER2-negative and HR-negative breast cancer benefited the most.

Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study

“…Adding bevacizumab to neoadjuvant chemotherapy has been shown to improve pCR rates in patients with HER2-negative breast cancer in the ARTemis, [24] GeparQuinto, [18,25] and NSABP B-40 17,21 studies, as well as in meta-analyses, [26] but in general, these improvements in pCR have not translated into improved long-term outcomes. The NSABP B-40 trial found that the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy significantly improved pCR in patients with HER2-negative, hormone receptor positive tumours [17] and this improvement in pCR was associated with higher OS but not DFS [21].…”

Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients

“…A recent meta-analysis, however, reports that in the neoadjuvant setting, the addition of Bev to standard chemotherapy significantly improves pCR, particularly in patients who are HER2-negative and hormone receptor-negative. [12] While these tumor characteristics are good predictors of pCR, the incorporation of other variables, such as germline SNPs in the angiogenic pathway, could potentially improve prediction models.…”

Effect of Lipodox in combination with bevacizumab in a patient with a metastatic malignant phyllodes breast tumor: A case report

“…A meta-analysis study of randomized controlled trials demonstrated that in the neoadjuvant setting, bevacizumab in combination with chemotherapy compared with chemotherapy alone increased the percentage of patients with non-metastatic breast cancer that achieved a pathological complete response. Bevacizumab was particularly effective in patients with human epidermal growth factor receptor 2-negative and hormone receptor-negative breast tumors ( 15 ). Malignant phyllodes tumors do not respond to chemotherapy or radiotherapy.…”