索拉非尼对HER2阴性转移性乳腺癌治疗效果Meta分析  

Sorafenib combined with chemotherapy for patients with HER2 negative metastatic breast cancer:A Meta-analysis

作　　者：贾晓晨[1] 孟文静[1] 何丽宏[1] 贾勇圣[1] 佟仲生[1] 

机构地区：[1]天津医科大学肿瘤医院乳腺肿瘤内科.国家肿瘤临床医学研究中心.乳腺癌防治教育部重点实验室.天津市肿瘤防治重点实验室.天津市恶性肿瘤临床医学研究中心,天津30060

出　　处：《中华肿瘤防治杂志》2017年第7期486-491,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家科技支撑计划(2015BAI12B15);天津市卫生局科技基金(2015KZ089)

摘　　要：目的索拉非尼是首个获准上市的多靶点酪氨酸激酶抑制剂。近年来探讨索拉非尼治疗HER2阴性转移性乳腺癌的临床试验不断开展,但试验结论并不一致。本研究通过Meta分析评价索拉非尼联合化疗治疗HER2阴性转移性乳腺癌的有效性和安全性。方法通过检索Pubmed、Embase以及Central等数据库,截止时间为2016-10,筛选索拉非尼联合化疗治疗HER2阴性的转移性乳腺癌的随机对照试验。试验结果应用Review Manager 5.3进行分析。结果纳入5个临床试验共计1 381例HER2阴性转移性乳腺癌患者,索拉非尼联合化疗与单纯化疗相比,使患者的疾病进展时间(time to progression,TTP)明显延长,2组之间差异有统计学意义,HR=0.77,95%CI为0.60~0.99,P=0.04;而无病生存期(progression-free survival,PFS;HR=0.83,95%CI为0.64~1.07,P=0.14)、总生存期(overall survival,OS;HR=1.06,95%CI为0.90~1.23,P=0.49)、客观反应率(objective response rate,ORR;RR=1.12,95%CI为0.97~1.30,P=0.14)2组之间差异无统计学意义。3~4度的手足综合征、乏力、皮疹、胃炎及贫血发生率明显增多,P<0.05;而中性粒细胞减少、血小板减少、腹泻以及高血压的发生率并未明显增加,P>0.05。结论相比单纯化疗,HER2阴性转移性乳腺癌患者可以从索拉非尼联合化疗治疗中获益,但手足综合征、皮疹等不良事件发生率有所增加。OBJECTIVE Sorafenib is an multikinase inhibitor investigated in a number of patients with solid tumors including metastatic breast cancer. However, the results of these clinical trials have been inconsistent. This study aimed to systematically evaluate the efficacy and safety of Sorafenib as salvage treatment for HER2 negative metastatic breast cancer by meta-analysis. METHODS Randomized controlled trials （RCTs） that compared the efficacy and safety of Sorafenib based therapy in patients with HER2 negative metastatic breast cancer with adjuvant chemotherapy alone were eligible. We searched from Pubmed, EMbase, The Cochrane Library, and Conference abstracts in ASCO and ESMO during last five years were also retrieved manually. The meta-analysis was conducted using Review Manager 5.3. RESULTS The final analysis included 5 studies involving a total of number 1 381 patients. The results revealed that compared with chemotherapy alone, Sorafenib-based therapy could improve TTP （HR=0.77,95%CI=0.60-0.99,P=0.04） ,however not the PFS （HR=0.83,95%CI=0.64-1.07,P=0.14） and OS （HR=1.06,95%CI=0.90-1.23,P=0.49）and ORR （RR=I. 12, 95;CI=0.97-1.30,P=0.14）. Meanwhile,the incidence of 3/4 adverse effects,including HFS, stomatitis, fatigue, rash and anemia were significantly increased in Sorafenib arm. CON- CLUSION Sorafenib can improve TTP for patients with HER2 negative metastatic breast cancer, Combined therapy was associ- ated with increased toxicities.

关 键 词：索拉非尼 多吉美 人类表皮生长因子受体 乳腺肿瘤 肿瘤转移 随机对照试验 META分析 

分 类 号：R737.9[医药卫生—肿瘤]