达拉非尼联合曲美替尼治疗黑色素瘤致皮肤不良反应的Meta分析

Meta-Analysis of Cutaneous Adverse Reactions Induced by Dabrafenib Combined with Trametinib in the Treatment of Melanoma

目的:系统评价达拉非尼联合曲美替尼治疗黑色素瘤致皮肤不良反应的发生率。方法:计算机检索PubMed、EMbase、Cochrane Library、Web of Science和中国知网、维普、万方、中国生物医学文献数据库,收集国内外公开发表的相关研究,检索时间为自建库至2020年12月。采用Stata 15.1软件计算皮肤不良反应的发生率,采用Rev Man 5.3软件评估所有等级皮肤不良反应的相对危险度(RR)。结果:共纳入10项研究,2623例患者。Meta分析结果显示:达拉非尼联合曲美替尼治疗黑色素瘤致所有等级皮肤不良反应的发生率为:皮疹22%[95%CI(0.19,0.26)]、瘙痒10%[95%CI(0.08,0.11)]、角化过度7%[95%CI(0.04,0.10)]、脱发5%[95%CI(0.04,0.07)]、皮肤乳头状瘤1%[95%CI(0.01,0.03)]、痤疮样皮炎10%[95%CI(0.06,0.14)]、皮肤鳞状细胞癌2%[95%CI(0.00,0.04)]、干性皮肤10%[95%CI(0.08,0.12)]和红斑11%[95%CI(0.09,0.13)];与单用BRAF抑制剂相比,达拉非尼联合曲美替尼降低了瘙痒、角化过度、脱发、皮肤乳头状瘤、皮肤鳞状细胞癌的发生率(P<0.05)。结论:达拉非尼联合曲美替尼治疗黑色素瘤患者常见的皮肤不良反应为皮疹;与单用BRAF抑制剂相比,联合用药显著降低了皮肤不良反应的发生。

Objective:To systematically evaluate the incidence of cutaneous adverse reactions induced by dabrafenib combined with trametinib in the treatment of melanoma.Methods:PubMed,EMbase,Cochrane Library,Web of Science,CNKI,VIP,Wanfang and China Biomedical Literature Database were searched by computer,and relevant published studies at home and abroad were collected.The retrieval period was from the establishment of the database to December 2020.Stata 15.1 software was used to calculate the incidence of cutaneous adverse reactions.RevMan 5.3 software was used to assess the relative risk(RR)for all grades of cutaneous adverse reactions.Results:A total of 10 studies involving 2623 patients were included.The incidence of cutaneous adverse reactions of all grades in the treatment of melanoma with dabrafenib combined with trametinib were as follows:exanthem 22%[95%CI(0.19,0.26)],pruritus 10%[95%CI(0.08,0.11)],hyperkeratosis 7%[95%CI(0.04,0.10)],alopecia 5%[95%CI(0.04,0.07)],cutaneous papilloma 1%[95%CI(0.01,0.03)],acneiform dermatitis 10%[95%CI(0.06,0.14)],cutaneous squamous cell carcinoma 2%[95%CI(0.00,0.04)],dry skin 10%[95%CI(0.08,0.12)]and erythema 11%[95%CI(0.09,0.13)].Compared with BRAF inhibitor alone,dabrafenib combined with trametinib reduced the incidence of pruritus,hyperkeratosis,alopecia,cutaneous papilloma,and cutaneous squamous cell carcinoma(P<0.05).Conclusion:Exanthem is a common cutaneous adverse reaction in patients with melanoma treated with darafenib combined with trametinib.Compared with BRAF inhibitor alone,the combination drug significantly reduced the occurrence of cutaneous adverse reactions.