7.2.1　Bevacizumab

Bevacizumab is a recombinant humanized monoclonal antibody against VEGF.It is the first VEGF inhibitor approved for marketing.It can prevent the biological effects of VEGF，destroy the formation of new blood vessels and reduce the tumor area by neutralizing VEGF.The supply of blood oxygen and other nutrients，which in turn inhibits tumor growth.Its half-life in the human body is 17 to 21 days.A large number of pre-clinical laboratory studies have shown that bevacizumab and chemotherapeutic drugs can reduce the density of tumor microvessels and have a synergistic effect.In the treatment of metastatic breast cancer，bevacizumab has shown significant anti-tumor effects，the most representative clinical study is an international multi-center open randomized phase Ⅲ clinical trial（ECOG2100）reported by Miller，The FDA of USA also approved bevacizumab（trade name Avastin）in combinationwith taxanes for first-line treatment of metastatic breast cancer in March 2008.

The results of three clinical studies（ECOG2100，AVADO，RIBBON-1 trial）laid the important role of bevacizumab in the first-line treatment of recurrent metastatic breast cancer.The results of these studies are basically the same，that is，bevacizumab no matter what a combination of chemotherapy drugs，its first-line treatment of recurrent metastatic breast cancer can surpass the efficacy of traditional chemotherapy，pfs significantly prolonged，and patients are well tolerated，no new treatment-related adverse reactions were found.However，these patients os did not improve.Whether US FDA has a controversy over the retention of bevacizumab in the treatment of breast cancer is a controversy.Can a significant improvement in surrogate endpoints（such as PFS）predict the benefit of early breast cancer patients in the absence of os benefit？(https://www.daowen.com)

Although bevacizumab can effectively treat a variety of malignant tumors，non-specific toxicity is less than chemotherapy drugs，the degree of adverse reactions is mild and generally tolerated，but serious adverse reactions may still occur in long-term use.The most common adverse reaction is grade 3 hypertension，proteinuria，gastrointestinal perforation，neutropenia，thrombosis in some patients，reversible posterior disease syndrome，nasal septal perforation，etc.These findings are unable to quell the debate about bevacizumab.The US FDA expert committee believes that although bevacizumab can delay tumor growth，there is no evidence to improve os and quality of life，but it also proves to be a serious and life-threatening risk.Therefore，on November 18，2011，the release of bevacizumab indications，for breast cancer was announced.but still approved for the treatment of certain tumors such as colon，lung，kidney and brain.In the NCCN guidelines，bevacizumab combined with paclitaxel is still recommended as a treatment for relapsed or metastatic breast cancer.However，In China，the application of bevacizumab in the treatment of breast cancer has not yet been approved In China.