Angiogenesis refers to the development of new blood vessels from the pre-existing beds containing the normal supply of blood vessels. Tumours are dependent on the formation of new blood vessels for their growth. Vascular-endothelial-growth-factor (VEGF) is a key molecule in promoting blood vessel growth. VEGF-targeting therapies are a new class of drugs designed to target a specific molecule. One of these drugs is bevacizumab (Avastin) which has been studied in clinical trials in metastatic breast cancer. Trials with other drugs are ongoing. Data are available from seven randomised trials, which evaluated the effect of bevacizumab on the primary endpoint in a total of 4032 patients with metastatic breast cancer. These patients were either-hormone receptor negative or had progressed on hormonal treatment. The primary end point was progression-free survival and secondary end points included overall survival, response rate measuring the change in size of the tumour, quality of life and toxicity of the treatment. Progression-free survival is considered a surrogate end point, i.e. a substitute for overall survival as an end point. The addition of bevacizumab to chemotherapy significantly prolongs progression-free survival and response rates in patients who have had previous chemotherapy and those who have not had previous chemotherapy for metastatic disease. The magnitude of this benefit is dependent on the type of chemotherapy used. Best results have been observed for the combination of weekly paclitaxel and bevacizumab in patients without prior chemotherapy for metastatic disease. Although progression-free survival was significantly longer with bevacizumab, there was no significant effect observed on either overall survival or quality of life. Quality of life is a direct measure of benefit to the patient. Adverse effects of bevacizumab in breast cancer are generally manageable, but may be serious and include increased frequencies of high blood pressure, blood clots in arteries and bowel perforations. However, overall rates of treatment-related deaths were lower in patients treated with bevacizumab. Because of the lack of effect on overall survival and quality of life, it is regarded as controversial whether bevacizumab is associated with a true patient benefit in spite of the increase in progression-free survival.
Treatments targeting blood vessels for metastatic breast cancer
July 11, 2012
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