Multicenter phase 2 study of trametinib for pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas

Plexiform neurofibromas (PNs) are seen in up to 50% of patients with neurofibromatosis type 1 (NF1). The multicenter TRAM-01 trial in Canada and the US evaluated the MEK inhibitor trametinib for pediatric patients with NF1 and inoperable PNs. Patients received oral trametinib once daily for a maximum of18 cycles of 28 days. Forty-six patients were recruited. The median age was 11.1 years (range 0.7-19.8). The median baseline tumor volume was 104.6 ml (range 16.3-650.1). Volumetric assessment demonstrated an overall response rate (decrease of volume at least 20%) in 47.8% of patients, with a median volume change of -19.3% (range -80.5 to 3.5). Forty-one patients (89.1%) completed the planned treatment. Three-year progression-free survival rate was 73.1% (95% CI 53.3-85.5) and 3-year event-free survival rate was 47.1% (28.8-63.5). The treatment was overall well tolerated. The authors conclude that trametinib is an effective treatment for pediatric NF1 patients with PNs.