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Evaluating larotrectinib for the treatment of advanced solid tumors harboring an NTRK gene fusion
Roberto Filippi1, Ilaria Depetris2, Maria Antonietta Satolli3
1Medical Oncology 1 - AOU Città Della Salute E Della Scienza Di Torino; Candiolo Cancer Institute, FPO - IRCCS Candiolo; Department of Oncology, University of Turin, Turin, Italy.
Abstract:
Introduction: Characteristic of some rare pediatric and adult malignancies, addiction to the NTRK oncogene family is also observed in a small fraction of common cancers. Inhibition of their protein products, the Trk kinases, proved a successful treatment strategy for these tumors.Areas covered: The current paper reviews the clinical development of larotrectinib, a selective inhibitor of the Trk kinase family, for the treatment of NTRK fusion-positive cancers. The manuscript includes an overview of the efficacy, safety, pharmacokinetics and pharmacodynamics. The authors sum up by providing the reader with their expert opinion on larotrectinib and its potential future use.Expert opinion: Larotrectinib showed tolerability and high efficacy, regardless of the primary site. In 2018, larotrectinib was granted by the Food and Drug Administration a tissue-agnostic approval for the treatment of solid tumors harboring an NTRK fusion. The major challenges will be the implementation of the screening for NTRK fusions in the general oncologic population, and the incorporation of larotrectinib into the therapeutic algorithms.
Insights
Larotrectinib effectively treats cancers with NTRK gene fusions, demonstrating high efficacy and tolerability. This targeted therapy, approved in 2018, offers a promising treatment option for various solid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The NTRK gene family is implicated in rare pediatric and adult malignancies, as well as a subset of common cancers.
- Inhibiting the Trk kinases, the protein products of NTRK genes, has emerged as a successful therapeutic strategy for these tumors.
Purpose of the Study:
- To review the clinical development of larotrectinib, a selective Trk kinase inhibitor.
- To provide an overview of larotrectinib's efficacy, safety, pharmacokinetics, and pharmacodynamics for NTRK fusion-positive cancers.
Main Methods:
- Review of clinical trial data and scientific literature on larotrectinib.
- Analysis of efficacy, safety, pharmacokinetic, and pharmacodynamic profiles.
Main Results:
- Larotrectinib demonstrated high efficacy and good tolerability across various primary cancer sites.
- The drug received tissue-agnostic approval from the FDA in 2018 for NTRK fusion-positive solid tumors.
Conclusions:
- Larotrectinib represents a significant advancement in treating NTRK fusion-positive cancers.
- Challenges include implementing NTRK fusion screening and integrating larotrectinib into treatment guidelines.
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