Meta分析：阿瓦斯汀对乳腺癌患者无益

MedSci补充：本荟萃分析表明对转移性乳腺癌来说，抗VEGF治疗，仍然存在争议。对患者的PFS来说，可能是有益的，但对OS，以及QOL尚未发现益处。但是VEGF已被中止用于乳腺癌，因此，本荟萃分析的价值是相对较小的。但是，阿瓦斯汀仍广泛用于治疗其它一些肿瘤的治疗。

      针对抗癌药阿瓦斯汀（贝伐单抗）一项的新研究显示，并不能延长转移性乳腺癌患者的总生存期（OS），也不能提高患者的生活质量，但可以改善患者的无进展生存（PFS）。相关研究报告7月11日发表在《科克伦图书馆》(Cochrane Database Syst Rev)上。

　　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，FDA取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，患者在使用阿瓦斯汀后，相关情况没有好转。

　　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。

原始链接:

Wagner AD, Thomssen C, Haerting J, Unverzagt S.Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer.Cochrane Database Syst Rev. 2012 Jul 11;7:CD008941.

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.