Comparative Toxicities of Neoadjuvant Chemotherapy With or Without Bevacizumab in HER2-Negative Breast Cancer Patients: A Meta-analysis

Background: The addition of bevacizumab to neoadjuvant chemotherapy improves the pathological complete response rate of human epidermal growth factor 2 (HER2)-negative breast cancer patients. However, the characteristics of adverse events associated with the use of bevacizumab should receive more attention from clinicians. Objective: This meta-analysis aimed to detect the adverse events of adding bevacizumab to neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone in HER2-negative breast cancer patients. Methods: PubMed, Cochrane Library, Web of Science, and EMBASE databases were systematically accessed to find eligible studies from January 1, 2000, to October 20, 2019. Reference lists were searched for additional studies. Pooled risk ratios for adverse events of bevacizumab were meta-analyzed. Results: Overall, 6 of 829 initially identified studies met the inclusion criteria, with 4681 patients randomized (2321 in the bevacizumab plus neoadjuvant chemotherapy group and 2360 in the neoadjuvant chemotherapy group). The incidence of grade ≥3 hypertension, left-ventricular dysfunction, mucositis, febrile neutropenia, infection, pain, hand-foot syndrome, hemorrhage, and neutropenia significantly increased in patients treated with bevacizumab plus neoadjuvant chemotherapy. However, adding bevacizumab to neoadjuvant chemotherapy was not associated with increasing the incidences of grade ≥3 proteinuria, dyspnea, heart failure, peripheral neurotoxicity, thrombosis, thrombocytopenia, fatigue, leucopenia, vomiting, nausea, and diarrhea. Conclusion and Relevance: Adding bevacizumab to neoadjuvant chemotherapy to treat HER2-negative breast cancer patients increased adverse events. However, most adverse events are clinically manageable. Patients, therefore, need to be monitored carefully for hypertension, left-ventricular dysfunction, mucositis, febrile neutropenia, infection, pain, hand-foot syndrome, hemorrhage, and neutropenia when treated with bevacizumab and neoadjuvant chemotherapy simultaneously.