Efficacy and safety of BRAF/MEK inhibitors in BRAFV600E-mutated anaplastic thyroid cancer: a systematic review and meta-analysis

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发表日期：

2024年5月6日

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Jonathan N. Priantti,
Natasha Maranhão Vieira Rodrigues,
Francisco Cezar Aquino de Moraes,
Allyson Guimarães da Costa,
Deborah Laredo Jezini,
Maria Izabel Ovellar Heckmann

摘要

Purpose

Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAF^V600E 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 BRAF^V600E ATC patients.

Methods

PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAF^V600E 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 BRAF^V600E ATC patients, especially in the neoadjuvant setting, with a tolerable safety profile. However, further clinical trials are warranted to investigate these findings.