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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.
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.
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.
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.
Same organ: Mediastinal germ cell tumour, Pleuropulmonary blastoma (types I, Ir, II and III), Type A and type AB thymoma, Type B1 and type B2 thymoma, Type B3 thymoma, Micronodular thymoma with lymphoid stroma, Adenocarcinoma of the lung, Squamous cell carcinoma of the lung, Large cell carcinoma of the lung, Sarcomatoid carcinoma of the lung, Adenosquamous carcinoma of the lung, Invasive mucinous adenocarcinoma of the lung, Adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung, Basaloid squamous cell carcinoma of the lung, Lymphoepithelial carcinoma of the lung, Pulmonary blastoma (adult), 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), Large cell neuroendocrine carcinoma of the lung, Thymoma (WHO types A, AB, B1, B2 and B3), Thymic carcinoma
Larotrectinib or entrectinib under their tumour-agnostic approvals; repotrectinib after resistance to either; chemoimmunotherapy as for driver-negative disease before or after.
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Repotrectinib is a preferred first-line ROS1 inhibitor because of its durability and coverage of resistance mutations, and it is also approved for NTRK fusion-positive tumours after prior TRK inhibitors.
Entrectinib is an approved tumour-agnostic TRK inhibitor with an advantage in patients with brain metastases, and it is also approved for ROS1-positive lung cancer.
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.
Query 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.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Avoid grapefruit.
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
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
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