Basket trial of TRK inhibitors demonstrates efficacy in TRK fusion-positive cancers

J Hematol Oncol. 2018 Jun 7;11(1):78. doi: 10.1186/s13045-018-0622-4.

Abstract

Unlike many conventional cancers with preferential patterns of oncogenic genetic alterations, TRK fusions resulting from NTRK1/2/3 genetic alterations drive oncogenic transformations in more than 20 different malignancies over diverse tissue/cell lineages, in both children and adults. A recent "basket" study of larotrectinib, a TRK inhibitor, has demonstrated significant efficacy in TRK fusion-positive tumors of all types from infants to the elderly. Here, we discuss the larotrectinib study and perspectives and challenges in developing "tumor-agnostic" targeted therapies in rare tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Clinical Trials as Topic
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasms / genetics*
  • Oncogene Proteins, Fusion / antagonists & inhibitors*
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*

Substances

  • Oncogene Proteins, Fusion
  • Pyrazoles
  • Pyrimidines
  • Receptor Protein-Tyrosine Kinases
  • larotrectinib