Background The MAPK pathway is a signal transduction cascade involved in the uncontrolled proliferation of many human cancers. A number of studies have shown that this pathway is constitutively activated in a high proportion of paediatric low grade gliomas (LGGs). Trametinib is a selective inhibitor of the MAPK pathway enzymes MEK1 and MEK2 used for some adult cancers. Targeting the MAPK pathway with trametinib appears to have reduced tumour sizes in some cases of inoperable paediatric astrocytomas.

Purpose To describe our experience in terms of acceptability and safety on the use of an extemporaneous oral solution of trametinib in paediatric patients with inoperable LGGs and other solid tumours with activated MAPK pathway.

Material and methods Patients were enrolled in the trametinib compassionate use programme of Novartis. Trametinib powder for oral solution was provided by the laboratory. When reconstituted, every 1 mL contained 0.05 mg of trametinib (recommended dose: 0.025 mg/kg, maximum 1 mg). Adverse events (AEs) were collected from the patients’ medical records. AEs were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) (4.03 version) 2010 of the National Institutes of Health. Information about taste, palatability, suitability of the volume and issues on the preparation of the extemporaneous solution were obtained by interviewing the patient or the caregiver.

Results 10 patients (aged 3–21 years) were treated with a median follow-up of 11 weeks. AEs reported included: 9 skin disorders (dry skin, pruritus, acneiform dermatitis and rash), 4 gastrointestinal disorders (abdominal pain, diarrhoea and constipation), 4 epistaxis, 2 paronychia and 2 increased liver enzymes. All AEs were classified as grade 1 or 2 according to the CTCAE and responded to supportive treatment. 7 of 10 said the oral solution had good palatability. None experienced swallowing difficulties. There were no problems with dosing or preparation of the extemporaneous solution. (Interim results to August 2016.)

Conclusion Trametinib powder for oral solution was well tolerated and accepted. All AEs were mild and responded to treatment. No dose adjustment or interruption of treatment was required. Trametinib appears to have a good toxicity profile. Safety and efficacy data from a larger population in a clinical trial is needed to confirm our results.

No conflict of interest