Larotrectinib can produce rapid and durable responses in children with NTRK fusion-positive central nervous system (CNS) tumors, according to updated trial results.

The results were presented at the 20th International Symposium on Pediatric Neuro-Oncology (ISPNO) by Karsten Nysom, MD, PhD, of University Hospital Rigshospitalet in Copenhagen, Denmark.

For this analysis, Dr Nysom and colleagues evaluated long-term follow-up data from the phase 1/2 SCOUT trial ( Identifier: NCT02637687) and the phase 2 NAVIGATE trial ( Identifier: NCT02576431). 

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The cohort included 28 patients who were younger than 18 years of age and had NTRK fusion-positive CNS tumors. Patients had high-grade gliomas (50%), low-grade gliomas (29%), and other tumors (21%). 

The median age of the patients at baseline was 7 (range, 1-17) years, and 61% were girls. Most patients (82%) had received prior systemic therapy, 61% had undergone surgery, and 43% had received radiotherapy.

The patients received larotrectinib at 100 mg/m2 twice daily. As of July 2021, the median time on treatment was 20 months (range, 1 to 39+ months), and the median time to response was 2 months (range, 1-4 months). 

The objective response rate (ORR) was 39%, with 11% of patients achieving a complete response and 29% achieving a partial response. 

Dr Nysom called the response rates “remarkable” because the ORR was 43% in patients with high-grade gliomas and 38% in patients with low-grade gliomas. 

The median duration of response was not reached at a median follow-up of 26 months. At 12 months, 64% of responders had retained a response. At 24 months, 53% of responders were still in response. 

The median follow-up was 28 months for both progression-free survival (PFS) and overall survival (OS). The median PFS was 22 months, and the median OS was not reached. 

The 12-month PFS rate was 63%, and the 24-month PFS rate was 50%. The 12-month OS rate was 85%, and the 24-month OS rate was 71%.

The most common treatment-related adverse events (TRAEs) were ALT increase, anemia, AST increase, and decrease in neutrophil count. Three patients reported grade 1-2 neurologic TRAEs.

Grade 3-4 TRAEs occurred in 3 patients as well (11%). These events included increased gamma-glutamyl transferase, hyperglycemia, hypernatremia, hyponatremia, and decreased neutrophil count. None of the patients discontinued treatment due to TRAEs.

Dr Nysom said these results support testing for NTRK fusions in pediatric patients with primary CNS tumors.

Disclosures: Both trials were sponsored by Bayer. The presenter disclosed affiliations with Bayer, Loxo Oncology, Y-mAbs, and EUSA Pharma. 


Nysom K, Doz F, Georerger B, et al. Long-term efficacy and safety of larotrectinib in paediatric patients with tropomyosin receptor kinase (TRK) fusion-positive primary central nervous system (CNS) tumours. Presented at ISPNO 2022; June 12-15, 2022. Abstract HGG-18.