MEK inhibition in adult patients with pilocytic astrocytomas

Pilocytic astrocytomas (PAs) are rare primary brain tumors in adults and exhibit worse outcomes compared with pediatric cases. Surgery is the primary therapeutic approach, whereas radiation therapy (RT) is reserved for symptomatic recurrence but is associated with substantial long-term toxicity. PAs are characterized by the activation of the mitogen-activated protein kinase (MAPK) signaling pathway and Mitogen-activated protein kinase kinase (MEK) inhibitors have demonstrated effectivity in pediatric populations, though data in adults remain limited. We retrospectively analyzed data of five adult patients (ages 30-79), four with PAs and one with PA with anaplastic transformation, that were administered trametinib, a MEK1/2 inhibitor. All tumors harbored somatic NF-1 mutations, with one germline NF-1 case. According to RANO 2.0 criteria, three patients achieved partial responses and two had stable disease, with neurological improvement in two cases. Median progression-free survival was 16.65 months, supporting MEK inhibition as an effective treatment strategy in adult PAs.