375P - Clinical outcomes of targeting therapy with BRAF/MEK inhibitors in patients with BRAF V600-mutated brain tumors

Background

Off-label use of BRAF/MEK inhibitors (i-BRAF/MEK) for the treatment of brain tumors with BRAF-V600 mutation (BRAF-V600m) has only been evaluated in a few studies, mainly case reports, which modest efficacy results. The aim is to describe the clinical outcomes of the treatment with i-BRAF/MEK in patients with BRAF V600m brain tumors.

Methods

All patients diagnosed with brain tumor who have been treated with an i-BRAF/MEK were included. Variables collected: gender, age, performance status (PS), diagnosis, line and duration of treatment. Effectiveness: response to treatment (RT), progression-free survival (PFS) and overall survival (OS). Safety: adverse reactions (AR) and dose reductions or temporary interruptions required due to toxicity.

Results

7 patients included (6 men), median age 25.0 years (IR:17.8-27.6) diagnosed with low-grade astrocytoma (n=1), pleomorphic xanthoastrocytoma (n=1), low-grade (n=2) and high-grade (n=1) glioma, glioblastoma (n=1) and ganglioglioma (n=1). PS: 1 (n=5) or 2 (n=2). Line of treatment of i-BRAF/MEK: 1^st (n=1), 2^nd (n=3), 3^rd and subsequent lines (n=4). 3 received dabrafenib in monotherapy, 1 trametinib in monotherapy and 3 dabrafenib/trametinib (1 of them previously received vemurafenib+cobimetinib). Median duration of treatment: 16.08 months (IR:9.00-24.88). After a median follow-up of 20 months, RT was: - Dabrafenib in monotherapy: partial response (n=3). 2 continue at the end of the study and the other, progressed at 21.8 months. -Trametinib: stable disease (n=1). -Dabrafenib/trametinib: disease progression (n=1, died 4 months later) and partial response (n=2). 1 subsequent progression disease (PFS 18.7 months). Median PFS 21.8 months CI95% (15.4-28.2) and OS 40.4 months CI95% (22.3 -58.5). Safety: main AR were dermatological (n=6), gastrointestinal (n=4), hepatic (n=2), other (metallic taste, fever, edema) (n=4). Due to toxicity, 4 patients required dose reductions, 4 temporary interruptions and 1 definitive suspension due tograde IV toxicity.

Conclusions

In our experience, i-BRAF/MEK therapy has been a good option in brain tumors with BRAF-V600m, with somewhat superior results in terms of efficacy but with a safety profile similar to those reported in previous studies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.