Regression of ETV6-NTRK3 Infantile Glioblastoma After First-Line Treatment With Larotrectinib

Abstract

This case study demonstrates that first-line treatment of a neurotrophic receptor tyrosine kinase (NTRK) fusion–positive infantile glioblastoma with larotrectinib, an NTRK inhibitor (NTRKi), was a safe and effective way to achieve tumor regression in our patient. An 18-month-old Saudi Arabian female presented with a history of right-sided weakness and partial seizures. Brain magnetic resonance imaging (MRI) revealed a large left frontal complex contrast-enhancing mass. Craniotomy for gross total resection (GTR) was performed, and histologic pathologic analysis revealed a diagnosis of glioblastoma. Postoperatively, the patient showed excellent recovery with no neurologic deficits. The tumor was then submitted for comprehensive genomic profiling. As a result of the expected poor survival, the patient’s family declined standard therapy, including chemotherapy and/or radiation therapy. Molecular analysis reported an ETV6-NTRK3 fusion, which can be targeted by larotrectinib, an oral tyrosine kinase (TRK) inhibitor. At the 3-month postresection follow-up, MRI showed local tumor recurrence. Given the results of molecular testing, the family agreed to initiate oral larotrectinib as a less invasive therapy. Follow-up MRI was performed 8 weeks after larotrectinib treatment and showed significant tumor regression, indicating a positive response to treatment with no reported adverse effects. This patient case highlights the importance of genomic profiling for pediatric brain tumors to identify targetable alterations. It further demonstrates the potential for TRK inhibitors as a first-line therapy for malignant pediatric brain tumors harboring TRK fusions.