易普利姆玛治疗晚期黑色素瘤有效性和安全性的Meta分析

Efficacy and safety of ipilimumab for treatment of advanced melanoma:a Meta-analysis

目的:系统评价易普利姆玛的有效性和安全性。方法:计算机检索PubMed,Cochrane Library,Embase,中国知网、万方和维普数据库。由2位研究者按照纳入和排除标准筛选文献、提取资料和质量评价后,采用RevMan 5.3软件进行Meta分析。结果:纳入4项随机对照试验,共2 622例病例。Meta分析结果显示:与对照组相比,易普利姆玛组1年无进展生存率(RR=0.94,95%CI:0.91~0.98,P=0.001)、1年总生存率(RR=0.79,95%CI:0.72~0.87,P<0.000 01)较高,具有统计学差异。2年无进展生存率无统计学差异(RR=0.99,95%CI:0.97~1.01,P=0.45)及3年总生存率(RR=0.93,95%CI:0.84~1.03,P=0.17)均无统计学差异。易普利姆玛组患者皮疹(RR=2.43,95%CI:1.64~3.61,P<0.000 01)、瘙痒(RR=2.35,95%CI:1.67~3.29,P<0.000 01)、腹泻(RR=1.82,95%CI:1.47~2.25,P<0.000 01)、结肠炎(RR=11.21,95%CI:6.20~20.30,P<0.000 01)、丙氨酸氨基转移酶增高(RR=3.57,95%CI:1.92~6.62,P<0.000 1)、天门冬氨酸氨基转移酶增高(RR=3.81,95%CI:2.85~5.09,P<0.000 01)的发生率均较高。结论:与对照组相比,易普利姆玛可提高患者1年无进展生存率、1年总生存率,但在2年无进展生存率及3年总生存率未显示出优势,且易普利姆玛增加了患者出现皮疹、瘙痒、腹泻、结肠炎和转氨酶升高的风险。

Objective： To conduct a Meta-analysis to evaluate the clinical efficacy and safety of ipilimumab for treatment of advanced melanoma. Methods： We searched the Pub Med,Cochrane Library,Embase,CNKI,Wanfang and VIP database. Two reviewers independently evaluated the quality of the included studies and extracted the data. Meta-analysis was performed by Rev Man 5. 3 software. Results： Four randomized controlled trials involving2 622 patients were included. The results of Meta-analyses showed that there were significant differences of the progression-free survival rate at 1 year（ RR = 0. 94,95% CI： 0. 91 - 0. 98,P = 0. 001）,overall survival rate at 1year（ RR = 0. 79,95% CI： 0. 72 - 0. 87,P 〈 0. 000 01） between the two groups. However,there were no significant difference of the progression-free survival（ PFS） rate at 2 years（ RR = 0. 99,95% CI： 0. 97 - 1. 01,P = 0. 45）and overall survival rate at 3 years（ RR = 0. 93,95% CI： 0. 84 - 1. 03,P = 0. 17） between the two groups. The incidences of cutaneous,gastrointestinal and hepatic adverse events showed significant differences between the two groups,including,rash（ RR = 2. 43,95% CI： 1. 64 - 3. 61,P 〈 0. 000 01）,pruritu（ RR = 2. 35,95% CI： 1. 67 -3. 29,P 〈 0. 000 01）,diarrhea（ RR = 1. 82,95% CI： 1. 47 - 2. 25,P 〈 0. 000 01）,colitis（ RR = 11. 21,95% CI：6. 20 - 20. 30,P 〈 0. 000 01）,increase in alanine aminotransferase（ RR = 3. 57,95% CI： 1. 92 - 6. 62,P 〈 0. 000 1）,and increase in aspartate aminotransferase（ RR = 3. 81,95% CI： 2. 85 - 5. 09,P 〈 0. 000 01）. Conclusion：Ipilimumab can increase progression-free survival rate at 1 year and overall survival rate at 1 year for advanced melanoma. However,ipilimumab showed no remarkable advantage in progression-free survival rate at 2 years andoverall survival rate at 3 years. Ipilimumab increased risks of pruritu,rash,diarrhea,colitis,and increase of alanine aminotransferase and aspartate aminotransferase.