The safety and efficacy of dabrafenib and trametinib in patients with glioma: A systematic review and meta-analysis.
Eur J Clin Pharmacol
; 80(5): 639-656, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38345637
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Pirimidinonas
/
Glioma
/
Imidazoles
Tipo de estudio:
Guideline
/
Prognostic_studies
/
Systematic_reviews
Límite:
Humans
Idioma:
En
Revista:
Eur J Clin Pharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Irán