Targeting BRAF V600E in Papillary Craniopharyngioma: Clinical Efficacy and Safety of Combined Braf-Mek Inhibition

Background: Papillary craniopharyngioma (PCP) is a rare central nervous system tumor with a high recurrence rate 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. Objectives To analyze patient demographics, presenting symptoms, comorbidities, prior treatments, tumor volumetric response, and the efficacy and safety of BRAF-MEK inhibitors in patients with BRAF V600E-mutated PCP. Methods: A systematic search was conducted across OVID Medline, Embase, Scopus, PubMed, and Web of Science following PRISMA guidelines. Studies reporting clinical outcomes of BRAF-MEK inhibitors in PCP were included. Results: Twenty-one studies involving 54 patients met the inclusion criteria, all receiving dual BRAF-MEK inhibitor therapy. Treatment was administered as neoadjuvant ( n = 11), adjuvant ( n = 34), or palliative therapy ( n = 9). Most studies were case reports, with two cohort studies (Brastianos et al., n = 16; De Alcubierre et al., n = 14) reporting high volumetric response rates of 93.8% and 92.9%, respectively. The median duration of targeted therapy was 5 months (range: 1.5–31), stratified as follows: 6 months (3–16) for neoadjuvant, 4.5 months (1.5–21) for adjuvant, and 7 months (2–31) for palliative therapy. At the end of treatment, the overall tumor volume reduction was 89% (20–100), with reductions of 90% (70–96) for neoadjuvant, 85% (20–95) for adjuvant, and 88% (25–100) for palliative therapy. Conclusion: BRAF-MEK dual inhibition demonstrates promising efficacy in both neoadjuvant and adjuvant settings for treating PCP, with encouraging tumor response rates and a manageable safety profile. While these targeted therapies offer a less invasive alternative, their long-term outcomes remain uncertain and require further validation through large-scale, comparative trials. Although disease control rates are promising, more data on long-term efficacy and optimal treatment strategies are needed to establish standardized protocols and optimize patient outcomes. Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany