NTRK fusion-positive non-small-cell lung cancer
NTRK fusion lung cancer is very rare and is treated with the same TRK-blocking pills approved for any cancer with the fusion: larotrectinib, entrectinib or repotrectinib shrink most tumours, including in the brain, so the point is to test broadly enough to find it.
Overview
NTRK1, NTRK2 and NTRK3 fusions drive a small share of many cancers, common in a few rare tumours (infantile fibrosarcoma, secretory carcinoma) and rare in common ones such as lung cancer. Larotrectinib was approved in November 2018 for any solid tumour with an NTRK fusion, the second tumour-agnostic approval after pembrolizumab for mismatch-repair deficiency, on a pooled response rate of 75 percent across tumour types in its phase 1 and 2 studies (NAVIGATE among them); entrectinib followed in August 2019 with a 57 percent pooled response rate and intracranial activity, and repotrectinib received a tumour-agnostic accelerated approval in June 2024, with activity against the solvent-front mutations that arise on the first two drugs.
In lung cancer specifically the numbers are small: lung cohorts within the larotrectinib and entrectinib programmes reported response rates of about 70 percent with responses in brain metastases, and the drugs are recommended first line or after chemotherapy. Dizziness, weight gain and paraesthesia from on-target TRK inhibition in the nervous system are the characteristic side effects. Checkpoint inhibitors and chemotherapy are used as for driver-negative disease when TRK inhibitors are exhausted.
Because the fusions are so rare, the practical question is testing: DNA panels miss some NTRK fusions, especially those involving NTRK2 and NTRK3 with large introns, so RNA sequencing or a combined panel is needed when no other driver is found. Open questions are the sequence of TRK inhibitors after resistance and whether next-generation inhibitors can avoid the neurological side effects.
State of the art
- Three TRK inhibitors approved for any tumour with an NTRK fusion, with response rates of 57 to 75 percent across cancers and brain activity.
- RNA-based testing recommended when no driver is found on a DNA panel.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Check before combiningFood and drink: Entrectinib
Avoid grapefruit.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
- Check before combiningHeart rhythm (QT): Entrectinib
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
See all on the product pages:CarboplatinEntrectinibPembrolizumabPemetrexedRepotrectinib·Printable cards in the navigator
Anatomy and lymph node drainage
- Central airways (squamous, small-cell)
- Periphery (adenocarcinoma)
- Apex (Pancoast)
- Pleura (mesothelioma)
- Thymus (anterior mediastinum)
- Nodes: hilar (N1)
- Nodes: mediastinal (N2)
- Nodes: supraclavicular (N3)
Central tumours arise in the large airways, peripheral ones in the alveoli; both drain to hilar then mediastinal nodes, and the pleural lining is a separate cancer site.
- Central airways (squamous, small-cell)
- Periphery (adenocarcinoma)NTRK1 fusion adenocarcinoma · NTRK2 or NTRK3 fusion adenocarcinoma (often missed by DNA-only panels)
- Apex (Pancoast)
- Pleura (mesothelioma)
- Thymus (anterior mediastinum)NTRK1 fusion adenocarcinoma · NTRK2 or NTRK3 fusion adenocarcinoma (often missed by DNA-only panels)
- hilar (N1)
- mediastinal (N2)
- supraclavicular (N3)
Same organ: Non-small-cell lung cancer, Lung cancer (all types), Small-cell lung cancer, Mesothelioma, Pleural mesothelioma, Thymoma and thymic carcinoma, Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours), Inflammatory myofibroblastic tumour (IMT), EGFR-mutated non-small-cell lung cancer, ALK-positive non-small-cell lung cancer, KRAS G12C-mutant non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer, MET exon 14 and MET-amplified non-small-cell lung cancer, RET fusion-positive non-small-cell lung cancer, BRAF V600E-mutant non-small-cell lung cancer, HER2-mutant non-small-cell lung cancer, PD-L1-high non-small-cell lung cancer without a driver mutation, Resectable stage I to III non-small-cell lung cancer, Unresectable stage III non-small-cell lung cancer, Limited-stage small-cell lung cancer, Extensive-stage small-cell lung cancer, Lung neuroendocrine tumours (typical and atypical carcinoid)
NTRK fusions occur in well under 1 percent of non-small-cell lung cancers, in adenocarcinoma regardless of smoking history; they are found mainly when broad RNA-based panels are used.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Larotrectinib or entrectinib under their tumour-agnostic approvals; repotrectinib after resistance to either; chemoimmunotherapy as for driver-negative disease before or after.
Subtypes & biomarkers
top- NTRK1 fusion adenocarcinoma
- NTRK2 or NTRK3 fusion adenocarcinoma (often missed by DNA-only panels)
- TRK inhibitor-resistant disease with solvent-front mutations (repotrectinib)
- NTRK1, NTRK2 and NTRK3 fusions by RNA sequencing (preferred) or DNA panel
- Pan-TRK immunohistochemistry as a screen
- NTRK resistance mutations (solvent front, gatekeeper) at progression
- Brain MRI
How often this target appears
- 2018Larotrectinib: tumour-agnostic approval for NTRK fusion cancers
- 2019Entrectinib approved for NTRK fusion tumours and ROS1 lung cancer
- 2024Repotrectinib gains tumour-agnostic accelerated approval for NTRK fusions
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 5 changes by month →- 2026-09-17This recordNTRK fusion-positive non-small-cell lung cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2024MilestoneRepotrectinibRepotrectinib gains tumour-agnostic accelerated approval for NTRK fusions
A milestone in how this cancer is treated.
- 2019MilestoneEntrectinibEntrectinib approved for NTRK fusion tumours and ROS1 lung cancer
A milestone in how this cancer is treated.
- 2018Trial resultNAVIGATENAVIGATE reported
ORR 75% by independent review in the first 55 pooled patients across 17 tumour types.
- 2018MilestoneLarotrectinibLarotrectinib: tumour-agnostic approval for NTRK fusion cancers
A milestone in how this cancer is treated.
What is in development for NTRK fusion-positive non-small-cell lung cancer, drawn from the whole corpus: 3 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials under way · 2
- A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements · phase 1/2 · Turning Point Therapeutics, Inc.
- Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangeme · phase 2 · Hoffmann-La Roche
Trials reported · 1
- NAVIGATE · phase 2 · 2018 · positive
Open problems and what is being done
Fusions are missed when only DNA panels are run.
Neurological side effects from TRK inhibition are class-wide.
and how the field plans to fix it →What is being done about thisSide effects and quality of lifeAvailable now- RepotrectinibApproved
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Side effects by symptom · Immune-related side effects · Toxicity compare · Survivorship planner.
Data specific to lung cancer come from small cohorts within basket trials.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Lausanne · hospital | Switzerland | none recorded | 0 | 509 | 9,176 | - | |
Brussels · cancer center | Belgium | none recorded | 0 | 489 | 8,689 | - | |
Aurora, CO · cancer center Programme: Oncogene-driven lung cancer, Lung cancer SPORE | United States | 0 | 483 | 13,480 | - | ||
Ljubljana · cancer center | Slovenia | none recorded | 0 | 187 | 2,566 | - | |
Philadelphia, PA · consortium | United States | none recorded | 0 | 165 | 1,237 | - | |
Neu-Isenburg · consortium | Germany | none recorded | 0 | 94 | 1,947 | none recorded | - |
Chicago, IL · consortium | United States | none recorded | 0 | 42 | 482 | - | |
Boulogne-Billancourt · government | France | none recorded | 0 | 32 | 240 | none recorded | - |
Silver Spring, MD · government | United States | none recorded | 0 | not matched | - | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with NTRK fusion-positive non-small-cell lung cancer but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about NTRK fusion-positive non-small-cell lung cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example NTRK1, NTRK2 and NTRK3 fusions by RNA sequencingor DNA panel, Pan-TRK immunohistochemistry as a screen, NTRK resistance mutationsat progression, Brain MRI), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include NTRK1 fusion adenocarcinoma, NTRK2 or NTRK3 fusion adenocarcinoma, TRK inhibitor-resistant disease with solvent-front mutations.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Advanced, first line or after chemotherapy
- For my situation (advanced, first line or after chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Larotrectinib or entrectinib under their tumour-agnostic approvals; repotrectinib after resistance to either; chemoimmunotherapy as for driver-negative disease before or after.
- Am I a candidate for Larotrectinib, Entrectinib, Repotrectinib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of NAVIGATE and Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangeme apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Repotrectinib, A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Fusions are missed when only DNA panels are run”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Neurological side effects from TRK inhibition are class-wide”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with NTRK fusion-positive non-small-cell lung cancer, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
5targets
4drugs
6companies
4pathways
2terms
5trials
3people
1Latest papers
topQuery for this cancer: (TITLE:"NTRK fusion-positive non-small-cell lung cancer" OR ABSTRACT:"NTRK fusion-positive non-small-cell lung cancer" OR TITLE:"NTRK-rearranged lung cancer" OR ABSTRACT:"NTRK-rearranged lung cancer" OR TITLE:"TRK fusion lung cancer" OR ABSTRACT:"TRK fusion lung cancer" OR TITLE:"NTRK1, NTRK2 or NTRK3 fusion NSCLC" OR ABSTRACT:"NTRK1, NTRK2 or NTRK3 fusion NSCLC") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about NTRK fusion-positive non-small-cell lung cancer, not a curated reading list.
Similar pages
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