Larotrectinib for the treatment of TRK fusion solid tumors

Theodore W Laetsch, Douglas S. Hawkins

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Introduction: TRK fusions occur across a wide range of cancers in children and adults. These fusions drive constitutive expression and ligand-independent activation of the TRK kinase and are oncogenic. Larotrectinib is the first highly potent and selective small molecule ATP competitive inhibitor of all three TRK kinases to enter clinical development. Areas covered: This review covers the current preclinical and clinical evidence for TRK inhibitors for TRK fusion cancers, focusing on larotrectinib. Expert commentary: Larotrectinib has demonstrated a remarkable 75% centrally confirmed objective response rate in patients with TRK fusion cancers in phase 1 and phase 2 clinical trials with generally mild side effects. Responses appear independent of the patient’s age, underlying histology, and specific fusion partner and are durable in many patients. Larotrectinib is likely to be the first FDA-approved histology-agnostic molecularly targeted therapy. The evolving role of molecular profiling of advanced cancers is discussed.

Original languageEnglish (US)
JournalExpert Review of Anticancer Therapy
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Neoplasms
Histology
Phosphotransferases
Clinical Trials, Phase I
Therapeutics
Adenosine Triphosphate
Ligands

Keywords

  • Larotrectinib
  • neurotrophin receptor
  • NTRK
  • TRK fusion
  • TRK inhibitor

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

Larotrectinib for the treatment of TRK fusion solid tumors. / Laetsch, Theodore W; Hawkins, Douglas S.

In: Expert Review of Anticancer Therapy, 01.01.2018.

Research output: Contribution to journalArticle

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