P11.24.B PRELIMINARY RESULTS OF THE TRAIN STUDY: TRAMETINIB IN NEUROFIBROMATOSIS TYPE 1 RELATED SYMPTOMATIC PLEXIFORM NEUROFIBROMAS

Abstract

Abstract BACKGROUND About half of the patients with neurofibromatosis type 1 (NF1) have plexiform neurofibromas (PN). PNs can cause pain, neurological deficit and cosmetic problems. The current standard treatment of PN is surgery, which is often difficult due to invasive growth and vascularisation. Recent data suggests promising effect of MEK inhibition on symptomatic PN in NF1. MATERIAL AND METHODS We started an open-label, single arm, phase 2 trial of trametinib 2 mg daily in 30 adults with NF1 and at least one symptomatic inoperable PN. The primary outcome measure is decrease in tumor volume of the PN target lesion, as measured on MRI every 6 months. A decrease of ≥20% will be considered as treatment response. The secondary outcome measures are pain, disfigurement, safety and toxicity. RESULTS Seventeen patients have been enrolled between July 2020 and July 2022 with an average follow-up duration of 16 months. In the 15 patients with at least 6 months follow-up, the average numeric pain rating scale (NRS-11) was reduced in 10/15 patients (67%) and a reduction of at least 3 points on the NRS-11 was achieved in 6/15 patients (40%). Tumor volume measurements have been completed in one patient with a PN in the left shoulder region. Tumor volume decreased from 160 cm3 to 100 cm3 (38%) after 18 months of treatment. The most common side effect was acneiform rash, which was present in 11/17 patients (65%). Four patients discontinued treatment permanently, 3 because of toxicity (acneiform rash (2) and CPK increase (1)) and one because of increased pain. Four cases of grade 3 adverse events have been reported: acneiform rash (2), hypertension (1) and asparatate aminotransferase increase (1). The only severe adverse event related to treatment was CPK increase grade 4, for which the patient was hospitalised for diagnostic work-up. Toxicity resolved completely in all patients after discontinuation of treatment. CONCLUSION From these preliminary results we can conclude that trametinib has a beneficial effect on PN related pain. Side effects are mild and toxicity resolved after discontinuation of treatment. At least one patient had a decrease in tumor volume of ≥20%.