Prospects of BRAF/MEK Inhibitor Therapy in Papillary Craniopharyngiomas with the BRAF V600E Mutation: A Scoping Review.

Craniopharyngiomas are locally aggressive, rare tumors that pose significant treatment challenges and often result in permanent neurological deficits. Since the discovery of the BRAF V600E driver mutation in papillary craniopharyngioma, several case reports have reported on the efficacy of BRAF inhibitors or the combination of BRAF and MEK inhibitors in treating papillary craniopharyngiomas with this mutation. However, the efficacy, safety, and optimal utilization of this emerging therapy for craniopharyngiomas remain unclear. We conducted a systematic review of published articles in PubMed, Scopus, and the Cochrane Library-CENTRAL, focusing on the efficacy and safety of BRAF/MEK inhibitor therapy in papillary craniopharyngiomas with the BRAF V600E mutation, covering publications from inception through June 2024. A total of 20 case reports and series involving 22 patients were included in the analysis. Combination therapy with BRAF/MEK inhibitors was employed in 81.8% of cases. Significant tumor reduction (≥80%) was observed in 18 of 21 cases, regardless of radiation therapy history, pretargeted therapy tumor volume, and tumor composition. The duration of tumor minimization ranged from 1 to 24 months (median: 5 months). Fever was the most commonly reported adverse event (28.6%), followed by dermatological symptoms (19%). Tumor recurrence was noted in 4 of 6 patients who did not receive additional treatment following the completion of targeted therapy; however, targeted therapy was effective in the cases in which it was resumed. This study provides critical insights into optimizing treatment strategies for papillary craniopharyngiomas and underscores the potential role of targeted therapies in enhancing patient outcomes.