文章：

BRAF与MEK抑制剂治疗BRAF突变型皮肤黑色素瘤患者相关不良事件的系统评价与荟萃分析

Treatment-Related Adverse Events in Individuals with BRAF-Mutant Cutaneous Melanoma Treated with BRAF and MEK Inhibitors: A Systematic Review and Meta-Analysis

原文发布日期：28 September 2025

DOI: 10.3390/cancers17193152

类型: Article

开放获取: 是

英文摘要：

Objectives: We conducted a systematic review of clinical trials and case reports analyzing the safety of the currently approved BRAF and MEK inhibitors in adults with cutaneous melanoma (CM), and a meta-analysis to estimate the pooled prevalence of treatment-related adverse events (TRAEs).Methods:We systematically searched six databases for studies publishedsince2009. The TRAE absolute frequencies reported in primary studies were aggregated using the Metaprop command in Stata 17, which calculates 95% confidence intervals (CIs) incorporating the Freeman–Tukey double arcsine transformation of proportions to stabilize variances within random-effect models. Methodological quality was assessed using the RoB 2 tool for randomized controlled trials (RCTs) and the ROBINS-I tool for non-randomized studies.Results: Twelve RCTs,thirteenprospective cohort studies (PCSs), and ten case reports were included. Meta-analysis was feasible for two regimens: vemurafenib 960 mg monotherapy and dabrafenib 150 mg twice daily plus trametinib 1–2 mg daily. The most common TRAEs during vemurafenib treatment were musculoskeletal and connective-tissue disorders (24%, 95% CI: 6–41%,p= 0.01), with arthralgia as the most prevalent (44%, 95% CI: 29–59%,p< 0.001), followed by rash (39%, 95% CI: 22–56%,p< 0.001). The most common TRAEs during dabrafenib plus trametinib were constitutional toxicities (classified in CTCAE as ‘General disorders and administration site conditions’; 25%, 95% CI: 14–37%,p< 0.001), with fatigue as the most prevalent (47%, 95% CI: 38–56%,p< 0.001), followed by pyrexia (40%, 95% CI: 26–54%,p< 0.001). Squamous cell carcinoma and keratoacanthoma were among the most frequent grade ≥ 3 cutaneous adverse events observed with vemurafenib therapy.Conclusions: Although additional large-scale studies are needed to corroborate these findings, each treatment has a distinct toxicity profile that should be considered when developing personalized risk-stratified treatment plans and in guiding healthcare resource allocation in melanoma care.

摘要翻译： 

目的：本研究对已发表的临床试验与病例报告进行系统性综述，分析当前获批用于成人皮肤黑色素瘤（CM）的BRAF及MEK抑制剂的安全性，并通过荟萃分析评估治疗相关不良事件（TRAEs）的合并发生率。 方法：系统检索自2009年以来发表于六大数据库的相关研究。采用Stata 17软件中的Metaprop命令对原始研究报告的TRAE绝对频率进行数据合并，通过Freeman-Tukey双重反正弦比例转换稳定随机效应模型内的方差，并计算95%置信区间（CIs）。方法学质量评估采用RoB 2工具评价随机对照试验（RCTs），使用ROBINS-I工具评价非随机研究。 结果：共纳入12项RCTs、13项前瞻性队列研究（PCSs）及10份病例报告。对两种治疗方案进行了可行性荟萃分析：维莫非尼960 mg单药治疗，以及达拉非尼150 mg每日两次联合曲美替尼1-2 mg每日一次治疗。维莫非尼治疗期间最常见的TRAEs为肌肉骨骼与结缔组织疾病（24%，95% CI：6-41%，p=0.01），其中关节痛发生率最高（44%，95% CI：29-59%，p<0.001），其次为皮疹（39%，95% CI：22-56%，p<0.001）。达拉非尼联合曲美替尼治疗最常见的TRAEs为全身性毒性（按CTCAE标准归类为“全身性疾病及给药部位状况”；25%，95% CI：14-37%，p<0.001），其中疲劳最为常见（47%，95% CI：38-56%，p<0.001），其次为发热（40%，95% CI：26-54%，p<0.001）。在维莫非尼治疗中观察到的≥3级皮肤不良事件以鳞状细胞癌和角化棘皮瘤最为常见。 结论：尽管仍需大规模研究验证，但每种治疗方案均具有独特的毒性特征，在制定个体化风险分层治疗计划及指导黑色素瘤医疗资源分配时应予以充分考虑。

原文链接：

Treatment-Related Adverse Events in Individuals with BRAF-Mutant Cutaneous Melanoma Treated with BRAF and MEK Inhibitors: A Systematic Review and Meta-Analysis