Efficacy and safety of BRAF-MEK dual inhibition in BRAF-V600E mutated papillary craniopharyngioma: a systematic review
Journal of Neuro-Oncology, vol.176, no.1, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Review
- Volume: 176 Issue: 1
- Publication Date: 2026
- Doi Number: 10.1007/s11060-025-05318-0
- Journal Name: Journal of Neuro-Oncology
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
- Keywords: Craniopharyngioma, BRAF, Inhibitors, MEK, Papillary, Systematic review, Targeted therapy
- Dokuz Eylül University Affiliated: Yes
Abstract
Purpose: Papillary craniopharyngioma (PCP) is a rare central nervous system tumor with high recurrence and significant morbidity. The BRAF V600E mutation has emerged as a potential target for treatment, with BRAF-MEK inhibitors showing promise in early studies. However, their efficacy and safety remain uncertain due to limited data from small-scale studies and case reports. This systematic review aims to evaluate the clinical outcomes of dual BRAF-MEK inhibitor therapy in BRAF V600E-mutated PCP. Methods: A systematic search of OVID Medline, Embase, Scopus, PubMed, and Web of Science was performed following PRISMA guidelines. Studies reporting clinical outcomes of BRAF–MEK inhibitors in PCP were included. Due to the predominance of case reports, a narrative systematic review was performed without meta-analysis. Results: Twenty-one studies involving 54 patients met inclusion criteria. Treatment was administered as neoadjuvant (n = 11), adjuvant (n = 34), or palliative (n = 9) settings. Most reports were case-based; two cohort studies (Brastianos et al., n = 16; De Alcubierre et al., n = 14) reported volumetric response rates of 93.8% and 92.9%, respectively. Common presenting symptoms included hypopituitarism (60.5%), visual changes (47.3%), and headache (44.7%). Median therapy duration was 5 months (range, 1.5–31); 6 months (3–16) for neoadjuvant, 4.5 months (1.5–21) for adjuvant and 7 months (2–31) for palliative use. Median tumor volume reduction was 89% overall (neoadjuvant 90%, adjuvant 85%, palliative 88%). Reported toxicities were generally manageable. Conclusion: Dual BRAF-MEK inhibition demonstrates robust tumor responses and a favorable safety profile across neoadjuvant, adjuvant, and palliative settings in PCP. These preliminary findings support further investigation to define long-term efficacy, safety, and integration into clinical protocols.