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

• Published in: Endocrine
• Main Authors: Priantti, Jonathan N, Rodrigues, Natasha Maranhão Vieira, de Moraes, Francisco Cezar Aquino, da Costa, Allyson Guimarães, Jezini, Deborah Laredo, Heckmann, Maria Izabel Ovellar
• Format: Journal Article
• Language: English
• Published: United States 06.05.2024
• Subjects: Anaplastic thyroid cancer; BRAFV600E; Targeted therapy; BRAF inhibitors; MEK inhibitors
• ISSN: 1559-0100; 1559-0100
• DOI: 10.1007/s12020-024-03845-w

Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAF 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 ATC patients. PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAF 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). 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, I  = 47%) and DCR was 85.39% (95% CI 78.10-92.68, I  = 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, I  = 84%) and 2-years OS rate was 52.08% (95% CI 35.71-68.45, I  = 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. Our study demonstrated BRAFi/MEKi have a decent activity for BRAF ATC patients, especially in the neoadjuvant setting, with a tolerable safety profile. However, further clinical trials are warranted to investigate these findings.