曲妥珠单抗联合化疗治疗HER-2阳性晚期胃癌的Meta分析

Trastuzumab combined with chemotherapy for Her-2 positive patients with advanced gastric cancer: a meta-analysis

目的系统评价曲妥珠单抗联合化疗治疗HER-2阳性晚期胃癌的有效性及安全性。方法计算机检索Clinical Trials.gov、Pub Med、EMbase、Web of Science、The Cochrane Library(2016年5期)、中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库、维普中文科技期刊数据库和主要会议数据库(ASCO和ESMO)等,搜集国内外公开发表的有关曲妥珠单抗联合化疗与单纯化疗比较治疗HER-2阳性晚期胃癌的随机和非随机的对照试验,检索时限均从建库至2016年5月。由2名研究者独立进行文献筛选、提取资料并评价纳入研究的偏倚风险后,采用Rev Man 5.3软件进行Meta分析。结果共纳入9个研究(包括3个RCT,6个非随机对照试验),合计1 034例HER-2阳性晚期胃癌患者。Meta分析结果显示,曲妥珠单抗联合化疗组(试验组)在完全缓解率[OR=2.76,95%CI(1.40,5.44),P=0.003]、部分缓解率[OR=1.81,95%CI(1.40,2.33),P<0.000 01]、总有效率[OR=2.09,95%CI(1.63,2.68),P<0.000 01]、疾病控制率[OR=2.20,95%CI(1.63,2.98),P<0.000 1]方面均优于对照组,而疾病稳定的差异无统计学意义[OR=0.87,95%CI(0.66,1.14),P=0.31];安全性方面,试验组的腹泻发生率[OR=1.51,95%CI(1.10,2.06),P=0.01]和皮疹发生率[OR=4.35,95%CI(1.25,15.10),P=0.02]明显高于对照组,而其余的不良反应两组差异均无统计学意义。结论曲妥珠单抗联合化疗较单纯化疗可提高HER-2阳性晚期胃癌患者的治疗有效率,但可能增加腹泻和皮疹发生率。受纳入研究质量和数量所限,本研究结论可能存在偏倚,需要开展更多高质量的研究予以验证。

Objective To systematically evaluate the safety and efficacy of trastuzumab combined with chemotherapy for HER-2 positive patients with advanced gastric cancer. Methods We searched ClinicalTrails.gov, PubMed, EMbase, Web of Science, The Cochrane Library （Issue 5, 2016）, CNKI, CBM, WanFang Data, VIP and major meeting proceeding databases （ASCO and ESMO） from inception to May 2016, to collect randomized controlled trials （RCTs） or non-RCTs about trastuzumab combined with chemotherapy versus chemotherapy alone for advanced gastric cancer. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was performed by using RevMan 5.3 software. Results Nine studies involving 1 034 HER-2 positive patients were included, of which three were RCTs and the other six were non-RCTs. Meta-analysis results indicated that the trastuzumab combined with chemotherapy group （the trial group） was superior to the chemotherapy alone group （the control group） in complete remission （OR=2.76, 95%CI 1.40 to 5.44, P=0.003）, partial remission （OR=1.81, 95%CI 1.40 to 2.33, P〈0.000 01）, overall response rate （OR=2.09, 95%CI 1.63 to 2.68, P〈0.000 01） and disease control rate （OR=2.20, 95%CI 1.63 to 2.98, P〈0.000 1）, while there was no statistical significances in stable disease （OR=0.87, 95%CI 0.66 to 1.14, P=0.31）. In terms of safety, the incidence of diarrhea （OR=1.51, 95%CI 1.10 to 2.06, P=0.01） and erythra （OR=4.35, 95%CI 1.25 to 15.10, P=0.02） in the trial group were higher than the control group. However, other adverse reactions were no significant differences in two groups. Conclusion Compared with chemotherapy alone, trastuzumab combined with chemotherapy in the treatment of HER-2 positive patients with advanced gastric cancer can significantly improve response rate, but it may increase the incidence of diarrhea and erythra. Because of the limited quality and quantity of the included studies, the above conclusion needs to be verified by conducting more high quality studies.