Abstract
Background
Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the literature and conducted meta-analyses to assess the efficacy and safety of these agents.
Methods
PubMed, Embase, and Scopus were searched from inception to September 2023 for studies examining dabrafenib and/or trametinib for gliomas. Outcomes included response rates (ORR, CR, PR), progression rates (PD), 6- and 12-month PFS, adverse events, and dosing modifications. Meta-analyses were conducted using random effect models.
Results
Nine studies met the inclusion criteria. Meta-analysis demonstrated overall response rates (ORR) of 50% (95% confidence interval (CI): 35–65%) for low-grade gliomas (LGG) and 40% (95% CI: 29–51%) for high-grade gliomas (HGG). Pooled ORR was 45% (95% CI: 36–54%) for both glioma grades. The complete response rate was 13% (95% CI: 05–27%) for HGG and 5% (95% CI: 1–10%) for both LGG and HGG. Six-month progression-free survival (PFS) rates reached 87% in LGG and 67% in HGG and a pooled 6-month PFS 78% (95% CI: 58–98%), declining at 12 months to 67% and 44%, respectively, with a pooled 12-month PFS 56% (95% CI: 34–79%). Grade 1–4 adverse events occurred in 100% of LGG and 63% of HGG patients.
Conclusions
Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes.
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Availability of data and material
The data that support the findings of this study are available from the corresponding author, M.A Habibi, upon reasonable request.
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Habibi MA, Fakhfouri A, Mirjani MS, Razavi A, Mortezaei A, Soleimani Y, Lotfi S, Arabi S, Heidaresfahani L, Sadeghi S, Minaee P, Eazi S, Rashidi F, Shafizadeh M, Majidi S (2024) Prediction of cerebral aneurysm rupture risk by machine learning algorithms: a systematic review and meta-analysis of 18,670 participants. Neurosurg Rev 47(1):34. https://doi.org/10.1007/s10143-023-02271-2. PMID: 38183490
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MA. H and MS.M contributed to the study conception and design, and edited the manuscript. MA.H and P.D and MH.A analyzed the data and wrote the first draft of the manuscript. O.A collected data. MA.H made a critical revision of the manuscript. All authors commented on previous versions of the manuscript and revised it. All authors read and approved the final manuscript.
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Habibi, M.A., Mirjani, M.S., Ahmadvand, M.H. et al. The safety and efficacy of dabrafenib and trametinib in patients with glioma: A systematic review and meta-analysis. Eur J Clin Pharmacol 80, 639–656 (2024). https://doi.org/10.1007/s00228-024-03635-3
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DOI: https://doi.org/10.1007/s00228-024-03635-3