Dabrafenib plus trametinib in low-grade versus high-grade gliomas: a systematic review and meta-analysis

Abstract

Abstract Background Dabrafenib plus trametinib is a novel targeted therapy for low-grade (LGG) and high-grade (HGG) gliomas. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of dabrafenib plus trametinib in LGG and HGG gliomas. Methods The electronic databases of PubMed/Medline, Scopus, Embase, and Web of Science were searched from inception to 5 September 2024. The meta-analyses, sensitivity analysis, publication bias, and meta-regression were performed through the R program. Results Nine studies with 313 patients were included. Our data demonstrated that dual blockage resulted in a pooled complete response (CR) rate of 10% (95% CI: 5—18%), partial response rate (PR) rate of 39% (95% CI: 32- 46%), stable disease (SD) rate of 36% (95% CI: 26-46%), and progressive disease (PD) rate of 17% (95% CI: 10- 29%). The PR was significantly higher in LGG (P = 0.03), and the PD was substantially lower in LGG (P < 0.01). Our results demonstrated a pooled overall objective response rate (ORR) of 47% (95% CI: 39—55%) without a significant difference in subgroups (P = 0.36). The meta-regression demonstrated that lower age, BRAF V600 mutation, longer dual blockage treatment duration, and history of prior resection were associated with more favorable outcomes in HGGs. Our meta-analysis revealed a pooled discontinuation due to adverse events (AE) rate of 12% (95% CI: 4- 31%). Conclusion Dabrafenib plus trametinib is associated with favorable outcomes in gliomas, especially among those with lower age, BRAF V600 mutation, longer dual blockage treatment duration, and history of prior resection. The co-administration of dabrafenib and trametinib was associated with more favorable outcomes among LGGs than HGGs.

Keywords

• Dabrafenib
• Trametinib
• Low-grade glioma
• High-grade glioma
• BRAF