# Larotrectinib

Source: https://onco.cc/drugs/larotrectinib/  
OnCo record `larotrectinib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first drug approved for a gene fusion regardless of where the cancer started; it works in about 75% of NTRK-fusion cancers, from infant fibrosarcoma to salivary and thyroid cancers.

## Summary

Drilon (NEJM 2018): 75% response across 17 tumour types; approved November 2018 as the second tumour-agnostic approval (after pembrolizumab MSI-H). Long durability (median DOR >40 months in updates); resistance via NTRK solvent-front mutations (G595R) addressed by repotrectinib and next-generation TRK inhibitors. Paediatric formulation.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-08
- Tags: gap-fill
- Brand: Vitrakvi
- Modality: Small-molecule pan-TRK inhibitor (first generation)
- Mechanism: Highly selective ATP-competitive inhibitor of TRKA/B/C (NTRK1/2/3) fusion kinases.
- Approvals: US 2018: Solid tumours with NTRK gene fusion without known acquired resistance mutation, metastatic or unresectable, adults and children; EU 2019: Same; UK 2020: NTRK fusion-positive solid tumours in adults and children, locally advanced or metastatic or where surgery would cause severe morbidity, with no satisfactory treatment options: NICE TA630 (27 May 2020) recommends it within the Cancer Drugs Fund under a managed access agreement; England (NICE) 2020: NTRK fusion-positive solid tumours, including colorectal cancer

## Notes

- Pancreatic cancer: NTRK fusions are rare drivers of KRAS wild-type pancreatic cancer; NICE NG85 (1.9.11) points to TA630, which makes larotrectinib available through the Cancer Drugs Fund while more data are collected. EU marketing authorisation 19 September 2019 (Vitrakvi).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Larotrectinib
- Drilon 2018 (NEJM): https://doi.org/10.1056/NEJMoa1714448
- Label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=larotrectinib
- NICE TA630: larotrectinib for NTRK fusion-positive solid tumours, Cancer Drugs Fund (27 May 2020): https://www.nice.org.uk/guidance/ta630
- EMA Vitrakvi product page: https://www.ema.europa.eu/en/medicines/human/EPAR/vitrakvi

## Connected records

- biomarkers: [NTRK1/2/3 gene fusion](https://onco.cc/biomarkers/ntrk-fusion/)
- cancers: [Ampullary cancer (ampulla of Vater)](https://onco.cc/cancers/ampullary/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Inflammatory myofibroblastic tumour (IMT)](https://onco.cc/cancers/inflammatory-myofibroblastic-tumour/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Metastatic cancer (cancer that has spread)](https://onco.cc/cancers/metastatic-cancer/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [NTRK fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ntrk-fusion-nsclc/), [Paediatric high-grade glioma (excluding diffuse midline glioma)](https://onco.cc/cancers/paediatric-high-grade-glioma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Papillary thyroid cancer](https://onco.cc/cancers/papillary-thyroid-cancer/), [Salivary gland cancers](https://onco.cc/cancers/salivary-gland/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Secretory carcinoma of the breast](https://onco.cc/cancers/secretory-carcinoma-breast/), [Thyroid cancer](https://onco.cc/cancers/thyroid/), [Uterine sarcoma](https://onco.cc/cancers/uterine-sarcoma/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [NTRK](https://onco.cc/targets/ntrk/)
- companies: [Bayer](https://onco.cc/companies/bayer/)
- terms: [Basket trial](https://onco.cc/terms/basket-trial/), [Colorectal cancer drugs in England: what NICE has recommended](https://onco.cc/terms/colorectal-uk-drug-access/), [Driver and passenger mutations: the refined somatic mutation theory](https://onco.cc/terms/driver-passenger-model/), [Gene fusion](https://onco.cc/terms/gene-fusion/), [Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)](https://onco.cc/terms/pancreatic-cancer-uk-drug-access/), [RACE for Children Act](https://onco.cc/terms/race-for-children-act/), [Tumour-agnostic (tissue-agnostic) approval](https://onco.cc/terms/tumour-agnostic/)
- trials: [A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children](https://onco.cc/trials/nct02637687/), [NAVIGATE](https://onco.cc/trials/navigate/), [NCI-COG Pediatric MATCH (APEC1621)](https://onco.cc/trials/pediatric-match/), [NCI-MATCH (EAY131)](https://onco.cc/trials/nci-match/), [Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer](https://onco.cc/trials/nct05725200/)
- key papers: [Larotrectinib in TRK fusion-positive cancers in adults and children](https://onco.cc/key-papers/paper-drilon-larotrectinib-nejm-2018/), [Metastatic Pancreatic Cancer: ASCO Guideline Update](https://onco.cc/key-papers/paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020/), [Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion](https://onco.cc/key-papers/paper-oreilly-hechtman-ntrk-fusion-pancreatic-larotrectinib-ann-oncol-2019/)
- institutions: [University of Colorado Cancer Center](https://onco.cc/institutions/colorado-cancer-center/)
- pathways: [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/), [Thyroid cancer (KEGG map)](https://onco.cc/pathways/thyroid-cancer-signalling/)
- drugs: [TruSight Oncology Comprehensive](https://onco.cc/drugs/trusight-oncology-comprehensive/)
- roadmaps: [Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first](https://onco.cc/roadmaps/paediatric-oncology-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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