Systematic review of neurotrophic tropomyosin-related kinase inhibition as a tumor-agnostic management strategy

Future Oncol. 2020 Feb;16(4):61-74. doi: 10.2217/fon-2019-0534. Epub 2020 Jan 16.

Abstract

Aim: To conduct a systematic review and meta-analysis feasibility of clinical, quality of life and economic evidence for neurotrophic tropomyosin-related receptor tyrosine kinases (NTRK) inhibitors in patients with NTRK gene fusion-positive tumors. Materials & methods: Databases were searched for studies on NTRK inhibitors in adult and pediatric patients. Results: 27 publications reported clinical data for seven interventions. Efficacy/safety data were available for two interventions only. Four trials each reported data for larotrectinib and entrectinib with pooled analyses reporting objective response rates of 75% (95% CI: 61-85) and 57.4% (43.2-70.8), respectively. No publications reported economic or quality of life evidence. Conclusion: Preliminary data demonstrate that NTRK inhibitors are well tolerated and show impressive clinical benefit; corroboration of existing studies and real-world data are required.

Keywords: NTRK; TKI; cabozantinib; entrectinib; larotrectinib; merestinib; neurotrophic tyrosine kinase receptors; systematic review; tyrosine kinase inhibitor.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Disease Management
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Quality of Life
  • Treatment Outcome
  • Tropomyosin / antagonists & inhibitors*
  • Tropomyosin / genetics
  • Tropomyosin / metabolism

Substances

  • Antineoplastic Agents
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Tropomyosin
  • Protein-Tyrosine Kinases