Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology

JCO Precis Oncol. 2024 May:8:e2300713. doi: 10.1200/PO.23.00713.

Abstract

Purpose: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes.

Patients and methods: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness.

Results: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause.

Conclusion: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.

MeSH terms

  • Adolescent
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Child
  • Child, Preschool
  • Clinical Trials as Topic
  • Female
  • Humans
  • Infant
  • Male
  • Neuroblastoma / drug therapy
  • Neuroblastoma / genetics
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyrazoles* / therapeutic use
  • Pyrimidines / therapeutic use
  • Receptor, trkA / antagonists & inhibitors
  • Receptor, trkA / genetics
  • Receptor, trkB / genetics
  • Receptor, trkC / genetics
  • Sarcoma / drug therapy
  • Sarcoma / genetics

Substances

  • larotrectinib
  • Pyrazoles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Receptor, trkA
  • Receptor, trkB
  • Receptor, trkC