Antitumor activity of larotrectinib in tumors harboring NTRK gene fusions

a short review on the current evidence

Biagio Ricciuti, Carlo Genova, Lucio Crinò, Massimo Libra, Giulia Costanza Leonardi

Research output: Contribution to journalArticle

Abstract

The development of deep-sequencing methods is now unveiling a new landscape of previously undetected gene fusion across different tumor types. Chromosomal translocation involving the NTRK gene family occur across a wide range of cancers in both children and adults. Preclinical studies have demonstrated that chimeric proteins encoded by NTRK rearrangements have oncogenic properties and drive constitutive expression and ligand-independent activation. Larotrectinib (ARRY470, LOXO101, Vitrakvi) is a highly and potent inhibitor of TRKA, TRKB, and TRKC, and has demonstrated rema rkable antitumor activity against TRK-fusion-positive cancers with a favorable side-effect profile in phase I/II clinical trials. In November 2018, the US Food and Drug Administration granted accelerated approval to larotrectinib for adult and pediatric patients with solid tumors harboring NTRK gene fusions without known acquired resistance mutation. In this review, we discuss the clinical activity and safety profile of larotrectinib, focusing on the clinical trials that led to its first global approval.

Original languageEnglish
Pages (from-to)3171-3179
Number of pages9
JournalOncoTargets and Therapy
Volume12
DOIs
Publication statusPublished - 2019

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Gene Fusion
Neoplasms
High-Throughput Nucleotide Sequencing
Genetic Translocation
Phase II Clinical Trials
Clinical Trials, Phase I
United States Food and Drug Administration
Clinical Trials
Pediatrics
Ligands
Safety
Mutation
Genes
Proteins

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Antitumor activity of larotrectinib in tumors harboring NTRK gene fusions : a short review on the current evidence. / Ricciuti, Biagio; Genova, Carlo; Crinò, Lucio; Libra, Massimo; Leonardi, Giulia Costanza.

In: OncoTargets and Therapy, Vol. 12, 2019, p. 3171-3179.

Research output: Contribution to journalArticle

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