82 Single centre experience of cutaneous toxicity associated with braf and mek inhibitor treatment in children

Background BRAF and MEK inhibitors are emerging therapies in childhood malignancy. The cutaneous side effects are well described in adult patients, but not in children. We undertook to document the spectrum of cutaneous side effects seen in children treated with these agents at our tertiary hospital, as well as the onset, duration and severity of the skin findings. Methods Retrospective chart review of children treated with either a BRAF (dabrafenib) or MEK inhibitor (trametinib). Basic demographic and clinical characteristics were collected from patient records and the skin findings assessed in collaborations with a paediatric dermatologist. Results Twenty-four children aged 1–16 years (mean 8.4 years) treated with either a BRAF (11) or MEK inhibitor (13) for BRAF -V600-mutant refractory or relapsed intracranial malignancy (8), neurofibromatosis type 1 (NF1)-associated optic glioma and neurofibroma (7), Langerhan cell histiocytosis (LCH) (3), or leptomeningeal melanocytosis/melanoma (3) were identified. One patient received combination BRAF/MEK inhibitor therapy. Mean treatment duration was 39 weeks (7–92) for BRAF and 19 weeks (7–37) for MEK inhibitor therapy. Six (54%) children treated with dabrafenib developed new melanocytic naevi (7–36 weeks), 5 of these also developed a persistent erythema nodsum-like (EN) eruption (onset 1–32 weeks) 2 diffuse alopecia, (onset 29 and 40 weeks) and single cases keratosis pilaris, an acneiform facial rash. Six (46%) children on a MEK inhibitor developed paronychia (onset 4–20 weeks), 5 of these also developing hair thinning (onset 4–17 weeks) and generalised xerosis (onset 2–8 weeks). Four patients (30%) developed acneiform eruptions. 1 child required dose reduction of therapy due to cutaneous side effects. Two patients discontinued treatment and one patient died because of disease progression. Conclusions Cutaneous adverse effects of BRAF and MEK inhibitor therapy are common and well tolerated in paediatric patients. Our experience is that prophylactic management is beneficial.