# Larotrectinib in TRK fusion-positive cancers in adults and children

Source: https://onco.cc/key-papers/paper-drilon-larotrectinib-nejm-2018/  
OnCo record `paper-drilon-larotrectinib-nejm-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The selective TRK inhibitor larotrectinib shrank tumours in three quarters of patients with NTRK fusions across 17 different cancer types and ages from infancy to old age, leading to the first tumour-agnostic approval of a targeted drug.

## Summary

Pooled analysis of 55 patients (adults and children) with TRK fusion-positive solid tumours across 17 tumour types from three phase 1 and 2 trials treated with larotrectinib.

Objective response was 75 percent by independent review with 71 percent of responses ongoing at one year, activity independent of tumour type, fusion partner or age, and mostly low-grade toxicity.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2018
- DOI: 10.1056/NEJMoa1714448
- Authors: Drilon A, Laetsch TW, Kummar S, et al.
- Findings: Objective response 75 percent across 17 tumour types.; 71 percent of responses ongoing at one year; 55 percent of patients progression-free at one year.
- What it means: NTRK fusion testing is now recommended in lung and other cancers without a common driver, and larotrectinib or entrectinib is the standard treatment when a fusion is found.
- Caveats: NTRK fusions are rare (under 1 percent) in lung cancer.; Acquired resistance mutations in the kinase domain develop; repotrectinib addresses some.

## Sources

- N Engl J Med 2018: https://doi.org/10.1056/NEJMoa1714448
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29466156/

## Connected records

- cancers: [NTRK fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ntrk-fusion-nsclc/)
- drugs: [Larotrectinib](https://onco.cc/drugs/larotrectinib/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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