Efficacy and safety of BRAF-MEK dual inhibition in BRAF-V600E mutated papillary craniopharyngioma: a systematic review.

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.