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An NTRK fusion joins one of three TRK kinase genes to a partner and drives cancers from infant fibrosarcoma to salivary and thyroid tumours, rare in common cancers but near-universal in a few rare ones. Larotrectinib, entrectinib and repotrectinib are approved for it regardless of tumour type.
NTRK1, NTRK2 and NTRK3 fusions (ETV6::NTRK3 in secretory carcinomas and infantile fibrosarcoma, LMNA::NTRK1 and TPM3::NTRK1 elsewhere) are best detected by RNA sequencing; DNA panels miss some NTRK2 and NTRK3 events because of long introns, and pan-TRK immunohistochemistry is a screen that needs molecular confirmation. Larotrectinib (2018) and entrectinib (2019) are labelled tumour-agnostically for solid tumours with an NTRK gene fusion without a known acquired resistance mutation, metastatic or where surgery would cause severe morbidity, with no satisfactory alternative or after progression; repotrectinib (2024) for NTRK fusion-positive solid tumours. FoundationOne CDx and Liquid CDx and TruSight Oncology Comprehensive are the listed companion diagnostics.
In plain words · Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it.
If your tumour carries an NTRK fusion, a TRK tablet (larotrectinib, entrectinib or repotrectinib) is on label whatever the type of cancer, once it has spread or cannot be removed without serious harm, and responses are frequent and often long. Ask whether the test included RNA sequencing, because DNA-only panels can miss these fusions.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
An in-frame fusion involving the kinase domain of NTRK1, NTRK2 or NTRK3 detected by RNA or DNA sequencing (pan-TRK IHC as a screen only), without a known acquired resistance mutation.
“NTRK1, NTRK2 and NTRK3 fusions”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| NTRK gene fusion without a known acquired resistance mutation | Larotrectinib | Metastatic cancer (cancer that has spread) | FDA | label |
| NTRK gene fusion in tumour or plasma | Entrectinib | Metastatic cancer (cancer that has spread) | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| FoundationOne CDx | Foundation Medicine | Solid Tumors - Tissue | Larotrectinib | P170019/S017 (10/23/2020) |
| FoundationOne CDx | Foundation Medicine | Solid Tumors - Tissue | Entrectinib | P170019/S014 (06/07/2022) |
| FoundationOne Liquid CDx | Foundation Medicine | Solid Tumors - Plasma | Entrectinib | P190032/S004 (12/22/2022) |
| TruSight Oncology Comprehensive | Illumina | Solid Tumors - Tissue | Larotrectinib | P230011 (08/21/2024) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
For gallbladder cancer the points that matter are that HER2 can disappear under HER2-directed pressure, that SMAD4 co-mutation predicts a worse response, and that sequencing at progression, not just at diagnosis, may be needed to guide the next line.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
The reference Western cohort for gallbladder cancer frequencies, deposited on cBioPortal as gbc_mskcc_2022, where the per-gene sample counts on OnCo were read. It supports panel testing at diagnosis: one patient in three has a targetable finding.
NTRK fusions are under 0.5% of pancreatic cancers but carry a tumour-agnostic approval; this case is the published proof that the label applies here.
Shares Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma, FoundationOne CDx / Liquid CDx, Tumour-agnostic (tissue-agnostic) approval and the tag biomarker.
Shares Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Tumour-agnostic (tissue-agnostic) approval, Thyroid cancer, Gallbladder cancer and the tag biomarker.
Shares Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, FoundationOne CDx / Liquid CDx, Tumour-agnostic (tissue-agnostic) approval, Gallbladder cancer and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Gene fusion, Biliary tract cancer (all types) and the tag biomarker.
Shares ALK fusion (ALK-positive), Gene fusion, Non-small-cell lung cancer and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Gene fusion and the tag biomarker.
Shares NRG1 gene fusion, Gallbladder cancer, Non-small-cell lung cancer and the tag biomarker.
Shares Tumour-agnostic (tissue-agnostic) approval, Gallbladder cancer, Metastatic cancer (cancer that has spread), Pancreatic ductal adenocarcinoma and the tag biomarker.