目的:约45%的间变性甲状腺癌(ATC)患者携带BRAFV600E突变,有资格接受BRAF和MEK抑制剂(BRAFi/MEKi)的靶向治疗(TT),然而,很少有数据支持这一点。因此,我们进行了系统评价和荟萃分析,调查了BRAFV600EATC患者应用BRAFi/MEKi的有效性和安全性.
方法:PubMed,Embase,系统检索Cochrane图书馆中BRAFV600EATC患者的BRAFi/MEKiTT。结果包括客观反应率(ORR),疾病控制率(DCR),总生存期(OS),无进展生存期(PFS),缓解持续时间(DOR)和不良事件(AE)。
结果:纳入了168例患者的9项研究。中位随访时间为2.0至47.9个月。75%的患者有IVc期。在汇总分析中,ORR为68.15%(95%CI55.31-80.99,I2=47%),DCR为85.39%(95%CI78.10-92.68,I2=0),平均DOR为14.4个月(95%CI4.6-14.4),平均PFS为6.7个月(95%CI4.7-34.2)。此外,1年OS率为64.97%(95%CI48.76-81.17,I2=84%),2年OS率为52.08%(95%CI35.71-68.45,I2=79%)。亚组分析显示,新辅助治疗组患者的1年和2年OS发生率较高,观察性研究报告的ORR发生率高于临床试验。没有发现新的或意外的不良事件。
结论:我们的研究表明BRAFi/MEKi对BRAFV600EATC患者具有良好的活性,特别是在新辅助治疗中,具有可容忍的安全性。然而,需要进一步的临床试验来研究这些发现.
OBJECTIVE: Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAFV600E mutation and are eligible for target therapy (TT) with BRAF and MEK inhibitors (BRAFi/MEKi), nevertheless, few data advocate for this. Hence, we\'ve conducted a systematic review and meta-analysis investigating the effectiveness and safety of BRAFi/MEKi in BRAFV600E ATC patients.
METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAFV600E ATC patients. Outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), duration of response (DOR) and adverse events (AEs).
RESULTS: Nine studies with 168 patients were included. Median follow-up ranged from 2.0 to 47.9 months. 75% of patients had stage IVc. In a pooled analysis, ORR was 68.15% (95% CI 55.31-80.99, I2 = 47%) and DCR was 85.39% (95% CI 78.10-92.68, I2 = 0), with a median DOR of 14.4 months (95% CI 4.6-14.4) and a median PFS of 6.7 months (95% CI 4.7-34.2). Moreover, 1-year OS rate was 64.97% (95% CI 48.76-81.17, I2 = 84%) and 2-years OS rate was 52.08% (95% CI 35.71-68.45, I2 = 79%). Subgroup analysis showed patients in the neoadjuvant setting had higher rates of 1 and 2-years OS and observational studies tended to report higher rates of ORR than clinical trials. No new or unexpected adverse events were found.
CONCLUSIONS: Our study demonstrated BRAFi/MEKi have a decent activity for BRAFV600E ATC patients, especially in the neoadjuvant setting, with a tolerable safety profile. However, further clinical trials are warranted to investigate these findings.