Long-term Efficacy and Safety of Larotrectinib in Pediatric Patients with Primary CNS and Non-Primary CNS TRK Fusion Tumors
Abstract
Introduction: Larotrectinib is a first-in-class, highly selective TRK inhibitor approved for tumor-agnostic treatment of patients with TRK fusion cancer. We report data on larotrectinib-treated pediatric patients with TRK fusion cancer.
Methodology: Patients aged <18 years with TRK fusion cancer enrolled in 2 larotrectinib clinical trials were included. Treatment responses were independent review committee (IRC)-assessed (RECIST v1.1 and RANO). Data cutoff: July 2023.
Results: There were 137 patients, including 38 patients with primary CNS tumors (47% high-grade glioma, 32% low-grade glioma, and 21% other) and 99 patients with non-primary CNS tumors (49% infantile fibrosarcoma, 41% soft tissue sarcoma, and 9% other). All patients were eligible for IRC efficacy analyses. ORR for patients with primary CNS tumors was 37% (95% CI 22–54): 3 CR, 11 PR, 17 SD, 5 PD, and 2 not evaluable. Medians for DoR, PFS, and OS were 17 months (95% CI 6–not estimable [NE]), 20 months (95% CI 11–51), and not reached (95% CI 33–NE), respectively. The 4-year OS rate was 60% (95% CI 42–78).
ORR for patients with non-primary CNS tumors was 86% (95% CI 77–92): 51 CR, 34 PR, 9 SD, 3 PD, and 2 not evaluable. Medians for DoR, PFS, and OS were 43 months (95% CI 27–NE), 40 months (95% CI 28–NE), and not reached (95% CI NE–NE), respectively. The 4-year OS rate was 90% (95% CI 84–96). Median time to response was 2 months (range 1–9) for all patients. Treatment-related adverse events were mostly Grade 1/2.
Conclusion: Larotrectinib demonstrated rapid and durable responses with a manageable safety profile in pediatric patients with primary CNS and non-primary CNS TRK fusion solid tumors. This supports the wider adoption of next-generation sequencing panels that include NTRK gene fusions when testing pediatric patients with solid malignancies including primary CNS tumors.
How to Cite
Chamdine O, Mascarenhas L, Doz F, Geoerger B, DuBois SG, Perreault S, et al. Long-term Efficacy and Safety of Larotrectinib in Pediatric Patients with Primary CNS and Non-Primary CNS TRK Fusion Tumors. OncoDaily Med J. 2025. doi:10.69690/ODMJ-018-0425-879