2026 Proffered Presentations
S280: TARGETING BRAF V600E IN PAPILLARY CRANIOPHARYNGIOMA: CLINICAL EFFICACY AND SAFETY OF COMBINED BRAF-MEK INHIBITION
Beste Gulsuna1; Baylee Stevens1; Belda Gülsuyu2; Ethan Wood3; Timurhan Aksoy4; Erika Santos Horta1; Ian F Dunn1; Christopher S Graffeo1; 1University of Oklahoma Health Science Center; 2University of California, San Francisco; 3College of Osteopathic Medicine, Oklahoma State University; 4Dokuz Eylül University Faculty of Medicine
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.
