一项针对全球畅销抗癌药阿瓦斯汀的新研究显示，这种药既不能延长乳腺癌患者的生命，也不能提高患者的生活质量。
美国食品和药物管理局曾在2008年通过简易程序批准阿瓦斯汀用于乳腺癌治疗。但临床试验显示，阿瓦斯汀并不能延长乳腺癌患者的生存期，且具有明显副作用，其中包括血压升高、易疲劳、白细胞异常等。去年11月，该局以不安全和无效为由吊销阿瓦斯汀治疗乳腺癌的许可。目前阿瓦斯汀仍可用于治疗肺癌、肾癌、结肠癌和直肠癌等。
美国等国的研究人员分析了7项针对4000多名转移性乳腺癌患者展开的随机对照试验。结果表明，阿瓦斯汀不能延长患者的生存时间。关于患者身体状况和日常生活满意度的调查也显示，患者在服用阿瓦斯汀后，相关情况没有好转。
相关研究报告已发表在医学杂志《科克伦图书馆》上。
阿瓦斯汀的化学名称为“贝伐单抗”，是一种单克隆抗体类药物。其研发理论认为，该药通过抑制血管内皮生长因子来阻断对肿瘤的血液供应，使肿瘤细胞无法在体内扩散，并能使化疗有效发挥作用。
关于阿瓦斯汀的“前世今生”，可点击阅读：罗氏阿瓦斯汀：身份尴尬的抗癌明星药
Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer
Anna Dorothea Wagner, Christoph Thomssen, Johannes Haerting, Susanne Unverzagt
Background
Vascular-endothelial-growth-factor (VEGF) is a key mediator of angiogenesis. VEGF-targeting therapies have shown significant benefits and been successfully integrated in routine clinical practice for other types of cancer, such as metastatic colorectal cancer. By contrast, individual trial results in metastatic breast cancer (MBC) are highly variable and their value is controversial.
Objectives
To evaluate the benefits (in progression-free survival (PFS) and overall survival (OS)) and harms (toxicity) of VEGF-targeting therapies in patients with hormone-refractory or hormone-receptor negative metastatic breast cancer.
Search methods
Searches of CENTRAL, MEDLINE, EMBASE, the Cochrane Breast Cancer Group's Specialised Register, registers of ongoing trials and proceedings of conferences were conducted in January and September 2011, starting in 2000. Reference lists were scanned and members of the Cochrane Breast Cancer Group, experts and manufacturers of relevant drug were contacted to obtain further information. No language restrictions were applied.
Selection criteria
Randomised controlled trials (RCTs) to evaluate treatment benefit and non-randomised studies in the routine oncology practice setting to evaluate treatment harms.
Data collection and analysis
We performed data collection and analysis according to the published protocol. Individual patient data was sought but not provided. Therefore, the meta-analysis had to be based on published data. Summary statistics for the primary endpoint (PFS) were hazard ratios (HRs).
Main results
We identified seven RCTs, one register, and five ongoing trials from a total of 347 references. The published trials for VEGF-targeting drugs in MBC were limited to bevacizumab. Four trials, including a total of 2886 patients, were available for the comparison of first-line chemotherapy, with versus without bevacizumab. PFS (HR 0.67; 95% confidence interval (CI) 0.61 to 0.73) and response rate were significantly better for patients treated with bevacizumab, with moderate heterogeneity regarding the magnitude of the effect on PFS. For second-line chemotherapy, a smaller, but still significant benefit in terms of PFS could be demonstrated for patients treated with bevacizumab (HR 0.85; 95% CI 0.73 to 0.98), as well as a benefit in tumour response. However, OS did not differ significantly, neither in first- (HR 0.93; 95% CI 0.84 to 1.04), nor second-line therapy (HR 0.98; 95% CI 0.83 to 1.16). Quality of life (QoL) was evaluated in four trials but results were published for only two of these with no relevant impact. Subgroup analysis stated a significant greater benefit for patients with previous (taxane) chemotherapy and patients with hormone-receptor negative status. Regarding toxicity, data from RCTs and registry data were consistent and in line with the known toxicity profile of bevacizumab. While significantly higher rates of adverse events (AEs) grade III/IV (odds ratio (OR) 1.77; 95% CI 1.44 to 2.18) and serious adverse events (SAEs) (OR 1.41; 95% CI 1.13 to 1.75) were observed in patients treated with bevacizumab, rates of treatment-related deaths were lower in patients treated with bevacizumab (OR 0.60; 95% CI 0.36 to 0.99).
Authors' conclusions
The overall patient benefit from adding bevacizumab to first- and second-line chemotherapy in metastatic breast cancer can at best be considered as modest. It is dependent on the type of chemotherapy used and limited to a prolongation of PFS and response rates in both first- and second-line therapy, both surrogate parameters. In contrast, bevacizumab has no significant impact on the patient-related secondary outcomes of OS or QoL, which indicate a direct patient benefit. For this reason, the clinical value of bevacizumab for metastatic breast cancer remains controversial.
