Long-term Efficacy and Safety of Larotrectinib in Pediatric Patients with Primary CNS and Non-Primary CNS TRK Fusion Tumors

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.