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BRAF and MEK inhibitor targeted therapy in papillary craniopharyngiomas: a cohort study
Dario De Alcubierre1,2, Grigorios Gkasdaris3, Margaux Mordrel4
1Department of Experimental Medicine, Sapienza University of Rome, Rome F-00161, Italy.
Objective:
Targeted therapy (TT) with BRAF/MEK inhibitors has emerged as a potential treatment in papillary craniopharyngiomas (PCPs). However, standardized data on large cohorts are lacking. Our study aimed to assess real-life efficacy and safety of BRAF/MEK inhibition in patients with PCPs.
Design:
Retrospective French multicenter study involving BRAF V600E-mutated PCP patients, treated with BRAF/MEK inhibitor combination dabrafenib and trametinib, from April 2019 to July 2023.
Methods:
Objective response and clinical and safety outcomes were assessed after 3 months and at the last available follow-up during TT.
Results:
Sixteen patients (8 females, mean age 50.5 ± 15.75 years), receiving either neoadjuvant therapy (NEO) for non-resectable tumors (n = 6), post-surgical adjuvant therapy (ADJ; n = 8), or palliative therapy (PAL) following failure of multimodal treatment (n = 2), were included.At the last follow-up (mean 7.6 ± 5.3 months), 12 patients showed subtotal response, 3 exhibited partial response, and 1 maintained stable disease. Mean volume reduction was 88.9 ± 4.4%, 73.3 ± 23.4%, and 91.8 ± 4.3% in the NEO, ADJ, and PAL groups, respectively.Targeted therapy resolved headaches in 5/5 patients and visual impairment in 6/9; 2/3 patients had improved neurological symptoms, 1/4 presented weight loss, and 2/14 recovered endocrine function.Targeted therapy was well-tolerated in 62.5% of cases; adverse events led to treatment discontinuation in 5 patients and definitive discontinuation in 3 cases.
Conclusions:
In this study, 94% of patients showed partial response or better to TT. Adverse events were acceptable. Further research is needed to establish standardized protocols; however, these results advocate for a NEO approach in invasive PCPs.
Insights
Targeted therapy with BRAF/MEK inhibitors shows high efficacy in papillary craniopharyngiomas (PCPs), with 94% of patients achieving partial response or better. This BRAF V600E treatment is well-tolerated and offers clinical benefits.
Area of Science:
- Neuro-oncology
- Molecular targeted therapy
- Craniopharyngioma research
Background:
- Papillary craniopharyngiomas (PCPs) are rare tumors with limited treatment options.
- Targeted therapy (TT) using BRAF/MEK inhibitors presents a promising avenue for PCPs harboring BRAF V600E mutations.
- Standardized data on large cohorts for this patient population are scarce.
Purpose of the Study:
- To evaluate the real-world efficacy and safety of BRAF/MEK inhibitor targeted therapy in patients with BRAF V600E-mutated PCPs.
- To assess objective response, clinical outcomes, and safety profiles of dabrafenib and trametinib in PCPs.
- To explore the potential of targeted therapy in different treatment settings (neoadjuvant, adjuvant, palliative).
Main Methods:
- Retrospective French multicenter study including 16 patients with BRAF V600E-mutated PCPs.
- Patients were treated with dabrafenib and trametinib between April 2019 and July 2023.
- Outcomes including objective response, clinical improvement, and adverse events were assessed at 3 months and last follow-up.
Main Results:
- 94% of patients achieved partial response or better (12 subtotal, 3 partial response).
- Significant tumor volume reduction observed across neoadjuvant (88.9%), adjuvant (73.3%), and palliative (91.8%) groups.
- Targeted therapy improved symptoms like headaches (100%) and visual impairment (66.7%), with generally acceptable tolerability.
Conclusions:
- BRAF/MEK inhibitor targeted therapy demonstrates significant efficacy in BRAF V600E-mutated PCPs, with high response rates and clinical benefits.
- The treatment was well-tolerated, suggesting its feasibility in clinical practice.
- Results support considering a neoadjuvant approach for invasive PCPs and highlight the need for standardized protocols.
