P14.26.A MEK INHIBITION IN ADULT PATIENTS WITH PILOCYTIC ASTROCYTOMAS HARBORING NF-1 MUTATIONS

Abstract BACKGROUND Pilocytic astrocytomas (PA) are rare primary brain tumors in adults and they demonstrate worse clinical outcomes compared with PAs in children. Surgery is the primary treatment option and radiation therapy (RT) is administered in the setting of symptomatic relapse after surgical excision. However, RT is associated with serious late side effects and an increased risk of malignant transformation and chemotherapy has demonstrated modest efficacy in adults with PAs. MATERIAL AND METHODS Molecularly, PAs are characterized by the activation of the mitogen activated protein kinase (MAPK) pathway. Mitogen-activated protein kinase kinase (MEK) inhibitors have been effective in the treatment of PAs in children but data in adult patients are lacking. Five adult patients in our institution (age range: 30-79 years), four with PAs and one with pilocytic astrocytoma with anaplastic transformation, were administered trametinib, a MEK 1-2 inhibitor. All of the patients’ tumours harboured somatic NF-1 mutations and only one of the patients had a germline NF-1 mutation. Response to trametinib was assessed according to RANO 2.0 criteria. RESULTS Three out of five patients had partial response (PR) and two experienced stable disease (SD) as best response to treatment. Two out of five patients had substantial neurological benefit. The median Progression-Free Survival (PFS) was 16.65 months (95% CI: 7.81 - 25.49) in our cohort. CONCLUSION These data demonstrate that MEK inhibition is active in adult patients with PAs and it can provide prolonged disease control. Thus, it can be used either as a salvage therapy or as an earlier systemic treatment option in order to prolong RT administration.