Treatment of Papillary Craniopharyngioma with BRAF V600E Mutation (CTNNB1-Negative)
Craniopharyngioma management is guided by molecular subtype. When pathological and molecular analysis identifies the papillary subtype with a confirmed BRAF V600E mutation and the absence of a CTNNB1 gene mutation, a distinct targeted treatment pathway is indicated.
Clinical Scenario
This protocol applies to papillary craniopharyngioma in which molecular testing has confirmed a BRAF p.V600E mutation and has excluded a CTNNB1 gene mutation. Molecular analysis for the BRAF p.V600E mutation is recommended for the diagnosis of papillary craniopharyngioma, and is systematically indicated when BRAF/MEK-directed treatment is under consideration. The presence of a BRAF V600E mutation is itself a marker pointing to the papillary subtype.
Treatment Approach
The evidence-based approach for this molecular profile involves a combination of BRAF- and MEK-inhibiting targeted therapies, the specific choice of which is to be discussed and decided by a dedicated multidisciplinary tumor board.
References
DOI: 10.1016/j.ando.2024.07.002
- Molecular analysis for the BRAF p.V600E mutation is recommended for the diagnosis of papillary craniopharyngioma, and systematically recommended if treatment with BRAF/MEK inhibitors is considered (strong).
- The presence of a BRAF V600E mutation points to PCP.
- For papillary craniopharyngiomas, combination of BRAF/MEK inhibiting therapies is a therapeutic option to be discussed by a dedicated tumor board (strong).
- As in other cancers with BRAF hotspot mutations, the combination of BRAF and MEK inhibitors is recommended to improve tolerability, reduce the risk of secondary skin cancers, reduce the risk of resistance, and increase anti-tumoral efficacy.