Background and Importance Entrectinib is an oral, CNS active, potent inhibitor of tyrosine approved for use in patients with NTRK gene fusion-positive solid tumours. Here, we report the antitumour activity and safety of entrectinib in a patient with central neurocytoma, an uncommon neoplasm with few drug treatment alternatives.

Aim and Objectives To summarise the overall safety and report the antitumour activity of entrectinib in a 50 year-old female with a primary central neurocytoma initially treated with surgery and radiotherapy. The patient began entrectinib after tumour NTRK fusion tested positive.

Material and Methods Diagnostic and follow-up tests and therapy were obtained by the review of medical records.

Foundation One NTRK fusion-positive tumour

Cardiac stress magnetic resonance imaging (MRI) with adenosine: Subclinical cardiotoxicity.

Results A 50 year-old female patient with a primary central neurocytoma. She received surgery as primary treatment in July 2020. After radiographic response and progression shortly, she was treated with adjuvant radiotherapy.

The tumour was tested for genetic mutations establishing a NTRK fusion-positive. Entrectinib treatment was authorised under compassionate use. The patient started treatment- in March 2021 at the full 600 mg daily dose.

After 1 month of treatment, the patient developed electrocardiogram and cardiac MRI alterations. She was diagnosed of subclinical cardiotoxicity grade 2 associated with entrectinib, given the temporal match. Dose was reduced to 400 mg daily and the patient was started on bisoprolol. In January 2022, MRI confirmed complete response. However, the patient was assessed by the neurologist and psychiatrist due to greater cognitive impairment and delusions. Duloxetine was started. In addition, entrectinib dose was reduced to 200 mg daily. In July 2022, entrectinib treatment was stopped and close follow-up was started. She experienced progressive neurologic improvement and less anxiety and depressive symptoms. In September 2022, MRI showed stable disease and after cardiologist and psychiatric evaluation, duloxetine and bisoprolol where withdrawn from treatment. In December 2022, clinical and radiologic stability were observed. Therefore, entrectinib was restarted at 200 mg daily with good tolerance until at least, today (October 2023).

Conclusion and Relevance Entrectinib has been shown to be active against those gene fusions in a primary CNS disease. However, it is still associated with moderate adverse events that require mandatory pharmacovigilance in our pharmacist daily practice.

Conflict of Interest No conflict of interest.