Department of Breast and Thyroid Surgery, West China Hospital, Sichuan University, Chengdu, China.
Department of Breast Disease, The Second People's Hospital of Sichuan, Chengdu, China.
J Breast Cancer. 2014 Mar;17(1):61-8. doi: 10.4048/jbc.2014.17.1.61. Epub 2014 Mar 28.
The aim of the study was to evaluate the efficacy and safety of combining sorafenib with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, American Society for Clinical Oncology abstracts, and European Society for Medical Oncology abstracts were searched. Randomized clinical trials that compared the efficacy and safety of sorafenib plus chemotherapy in patients with HER2-negative advanced breast cancer with placebo plus chemotherapy were eligible. The endpoints were progression-free survival (PFS), overall survival (OS), time to progression (TTP), duration of response (DOR), overall response rate (ORR), clinical benefits, and adverse effects. The meta-analysis was performed using Review Manager 5.2.6 (The Nordic Cochrane Centre), and the fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1), further analysis (subgroup analysis, sensitivity analysis, or random-effect model) was performed to identify the potential cause. The results are expressed as hazard ratios or risk ratios, with their corresponding 95% confidence intervals.
The final analysis included four trials comprising 844 patients. The results revealed longer PFS and TTP, and higher ORR and clinical benefit rates in patients receiving sorafenib combined with chemotherapy compared to those receiving chemotherapy and placebo. OS and DOR were similar in the two groups. Meanwhile, the incidence of some adverse effects, including hand-foot skin reaction/hand-foot syndrome, diarrhea, rash, and hypertension, were significantly higher in the sorafenib arm.
Sorafenib combined with chemotherapy may prolong PFS and TTP. This treatment was associated with manageable toxicities, but frequent dose interruptions and reductions were required.
本研究旨在评估索拉非尼联合化疗治疗人表皮生长因子受体 2（HER2）阴性晚期乳腺癌患者的疗效和安全性。
检索 MEDLINE、EMBASE、Cochrane 中央对照试验注册库、美国临床肿瘤学会摘要和欧洲肿瘤内科学会摘要。符合条件的随机临床试验比较了索拉非尼联合化疗与安慰剂联合化疗治疗 HER2 阴性晚期乳腺癌患者的疗效和安全性。终点包括无进展生存期（PFS）、总生存期（OS）、进展时间（TTP）、缓解持续时间（DOR）、总缓解率（ORR）、临床获益和不良反应。使用 Review Manager 5.2.6（北欧 Cochrane 中心）进行荟萃分析，采用固定效应模型加权的 Mantel-Haenszel 方法。当发现存在显著异质性时（p<0.1），进行进一步分析（亚组分析、敏感性分析或随机效应模型）以确定潜在原因。结果表示为风险比或风险比，及其相应的 95%置信区间。
最终分析包括四项临床试验，共纳入 844 例患者。结果显示，与接受化疗和安慰剂的患者相比，接受索拉非尼联合化疗的患者 PFS 和 TTP 更长，ORR 和临床获益率更高。两组患者的 OS 和 DOR 相似。同时，索拉非尼组一些不良反应（包括手足皮肤反应/手足综合征、腹泻、皮疹和高血压）的发生率显著升高。
索拉非尼联合化疗可能延长 PFS 和 TTP。这种治疗方法具有可管理的毒性，但需要频繁中断和减少剂量。
