Trametinib Treatment for Early-Stage Extracranial Arteriovenous Malformations: A Multicenter, Prospective, Single-Arm Pilot Study.

Background: Extracranial arteriovenous malformations (eAVMs) are progressive vascular anomalies for which conventional therapies are rarely curative. Few standard therapies have been developed for early-stage eAVMs. In particular, the efficacy and safety of trametinib for treating early-stage childhood eAVM are unclear.

Objective: To assess the efficacy and safety of trametinib treatment for early-stage eAVMs over 12 months of treatment.

Method: Patients with early-stage eAVM received trametinib for at least 12 months. All participants underwent clinical and radiological follow-up, including quantitative (skin temperature, peak arterial velocity, skin color) and qualitative (DSA) assessments.

Results: Therapeutic outcomes of the 26 patients included the following clinical responses: an average skin lesion blanching rate of 53.5%, a decrease in skin temperature of nearly 1°C, a decrease in peak arterial blood flow velocity of 74%, and 50% of the patients achieving more than 50% devascularization. Patients with somatic KRAS/MAP2K1 mutations had more significant clinical improvement than patients with RASA1/EPHB4 germline mutations did. Trametinib was well tolerated, with most adverse events assessed as grade 1/2.

Conclusion: This pilot study demonstrates short term efficacy and safety in the treatment of early-stage eAVMs utilizing trametinib. Further study is needed to evaluate long term outcomes.