Tan Qi-Xing, Qin Qing-Hong, Lian Bin, Yang Wei-Ping, Wei Chang-Yuan
Breast Surgery Department, Tumor Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Exp Ther Med. 2014 May;7(5):1420-1426. doi: 10.3892/etm.2014.1603. Epub 2014 Mar 5.
A standard systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) is yet to be identified. Sorafenib has been developed for the treatment of solid tumors, including breast cancer, as an oral multikinase inhibitor with antiangiogenic and antiproliferative activity. The aim of the present study was to assess the efficacy and safety of sorafenib in patients with HER2-negative ABC by performing a meta-analysis. A literature search was applied to databases, including PubMed, EMBASE, the Cochrane Library Databases, American Society of Clinical Oncology and the European Society for Medical Oncology, with the search terms 'advanced breast cancer' and 'sorafenib' and relevant studies were selected for analysis. The data extracted from the selected studies included progression-free survival (PFS), time to progression (TTP), overall survival (OS) and overall response rate (ORR). Major adverse events (AEs) were also analyzed. A total of four randomized controlled trials containing 844 cases were identified. Combined results revealed that when compared with chemotherapy (or with anti-hormone receptor therapy) alone, sorafenib-based therapy significantly increased the PFS [hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.54-1.02] and TTP (HR, 0.74; 95% CI, 0.50-0.97), but not the OS (HR, 0.95; 95% CI, 0.75-1.15) and ORR (relative risk, 1.19; 95% CI, 1.01-1.39). In addition, the incidence of grade 3/4 AEs, including hand-foot skin syndrome, anemia, fatigue, rash and stomatitis, were significantly increased in patients that received sorafenib-based therapy. Therefore, the results from the current meta-analysis indicated that sorafenib-based therapy improved the PFS and TTP in patients with HER2-negative ABC, but not the OS and ORR. In addition, combination treatment was associated with increased toxicities and frequently required dose reductions.
针对人表皮生长因子受体2（HER2）阴性晚期乳腺癌（ABC）患者的标准全身治疗方案尚未确定。索拉非尼作为一种具有抗血管生成和抗增殖活性的口服多激酶抑制剂，已被开发用于治疗包括乳腺癌在内的实体瘤。本研究的目的是通过进行荟萃分析来评估索拉非尼在HER2阴性ABC患者中的疗效和安全性。对包括PubMed、EMBASE、Cochrane图书馆数据库、美国临床肿瘤学会和欧洲医学肿瘤学会在内的数据库进行文献检索，检索词为“晚期乳腺癌”和“索拉非尼”，并选择相关研究进行分析。从所选研究中提取的数据包括无进展生存期（PFS）、疾病进展时间（TTP）、总生存期（OS）和总缓解率（ORR）。还分析了主要不良事件（AE）。共确定了四项包含844例病例的随机对照试验。综合结果显示，与单纯化疗（或抗激素受体治疗）相比，基于索拉非尼的治疗显著提高了PFS[风险比（HR），0.78；95%置信区间（CI），0.54 - 1.02]和TTP（HR，0.74；95%CI，0.50 - 0.97），但未提高OS（HR，0.95；95%CI，0.75 - 1.15）和ORR（相对风险，1.19；95%CI，1.01 - 1.39）。此外，接受基于索拉非尼治疗的患者中，3/4级AE的发生率显著增加，包括手足皮肤综合征、贫血、疲劳、皮疹和口腔炎。因此，当前荟萃分析的结果表明，基于索拉非尼的治疗改善了HER2阴性ABC患者的PFS和TTP，但未改善OS和ORR。此外，联合治疗与毒性增加相关，且经常需要降低剂量。
