Medical Oncologist
Tumour-agnostic targeted therapy
NTRK Fusion: — One Drug Class Across Many Cancer Types
An NTRK fusion is a gene change found in many different cancer types. When it is present, a class of targeted drugs called TRK inhibitors can be used — and they work regardless of where in the body the cancer started.
Medically reviewed by Dr. T. Raghavender Reddy, Medical Oncologist, MBBS · DM (Medical Oncology) · MD (Radiation Oncology) · Last reviewed August 2026
- Cancer type does not decide eligibility — Any solid tumour with a confirmed NTRK fusion may be considered for TRK inhibitor therapy, whether it started in the lung, colon, thyroid, or elsewhere.
- Testing comes first — A biomarker test on your tumour tissue is needed to confirm whether the fusion is present. Without it, treatment cannot be planned.
- Oral treatment, not infusion — TRK inhibitors are taken as tablets at home, not as intravenous chemotherapy in a clinic.
- Rare overall, common in some cancers — NTRK fusions are uncommon in the most frequent adult cancers but occur at much higher rates in some rarer tumour types.
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An NTRK fusion is a gene rearrangement that activates cancer growth regardless of where the tumour started. TRK inhibitors are the targeted therapy class designed for it. They are approved for use across many cancer types — lung, colon, thyroid, salivary gland — provided the NTRK fusion is confirmed by biomarker testing.
How does NTRK testing and treatment work, step by step?
Biomarker testing is ordered
Your oncologist orders NTRK fusion testing on your tumour tissue. RNA-based next-generation sequencing is the most reliable method for detecting fusions.
The existing biopsy sample is used
Testing is usually done on tissue removed during your original biopsy. A fresh biopsy is only needed if the original sample is too small or unavailable.
The result is reviewed
A positive result means an NTRK fusion is present. Your oncologist identifies which gene is involved — NTRK1, NTRK2, or NTRK3 — and explains what this means for treatment options.
A TRK inhibitor is considered
If a fusion is confirmed and the drug is appropriate for your situation, your oncologist discusses starting a TRK inhibitor. NCCN and ASCO guidelines support their use in NTRK fusion-positive solid tumours regardless of cancer type.
You take the drug at home
TRK inhibitors are oral tablets taken daily. You do not need to attend a clinic for an infusion. Regular blood tests and scans monitor how treatment is working.
What is an NTRK fusion, and why does the drug work across cancer types?
Your NTRK genes normally help nerve cells grow and survive. In some cancers, a portion of an NTRK gene breaks off and joins with a different gene. The result is a permanently active protein that keeps telling cells to divide.
This fused gene drives cancer growth in the same way whether the tumour started in the lung, thyroid, colon, or salivary gland. The target for the drug is always the same protein. That is why a TRK inhibitor can work across different cancer types — the mutation, not the organ, is what matters.
NTRK fusions are uncommon in the most frequent adult cancers but are found at much higher rates in secretory carcinomas, infantile fibrosarcoma, and certain thyroid tumours. Because they are rare overall, they are easy to miss without dedicated molecular testing.
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Which TRK inhibitors are used, and how do they differ?
Two TRK inhibitors are approved by major regulatory bodies for NTRK fusion-positive solid tumours. Both are oral tablets taken daily. Neither requires clinic infusion.
Larotrectinib targets the TRK proteins produced by fused NTRK genes. It is approved for NTRK fusion-positive solid tumours in adults and children. Response rates in patients with confirmed NTRK fusions are described as high in NCCN guidance. It crosses the blood-brain barrier and has activity against cancer that has spread to the brain.
Entrectinib targets TRK proteins and also ROS1 and ALK. It is approved for NTRK fusion-positive solid tumours and separately for ROS1-rearranged lung cancer. Like larotrectinib, it crosses the blood-brain barrier and is active against brain metastases.
The choice between them depends on the specific NTRK gene involved, whether brain metastases are present, your other medications, and local availability. Your oncologist will discuss which is appropriate for your situation.
Neither drug is a broad-spectrum cancer treatment. Both work only where an NTRK fusion has been confirmed by testing.
If your report shows an NTRK fusion: ask your oncologist these things
- Ask which NTRK gene is involved and whether the result is a confirmed fusion or a variant of uncertain significance.
- Ask whether larotrectinib or entrectinib is available and appropriate for your cancer type and stage.
- Tell your oncologist every medication and supplement you take — TRK inhibitors interact with some common drugs.
- Ask whether brain imaging has been done or is needed, as this affects which drug may be preferred.
- Confirm when the first response-assessment scan is planned and what it will measure.
- Ask what the next option is if the drug stops working — second-generation TRK inhibitors exist for resistance cases.
What should you expect while taking a TRK inhibitor?
TRK inhibitors are generally better tolerated than chemotherapy. Common side effects include fatigue, dizziness, nausea, and raised liver enzymes. Most are mild to moderate and manageable with dose adjustment.
Some people notice dizziness or unsteady walking. These neurological effects are usually handled by adjusting the dose rather than stopping treatment altogether.
The drug is taken every day, not in cycles. There is no recovery week. Most people continue daily activities while on treatment.
Response assessment — usually by scan — is done periodically. Your oncologist will explain what the scan is looking for and when to expect the result. PET-CT and other imaging are coordinated with partner imaging centres at CION.
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Common questions
Frequently asked questions
Can any cancer type have an NTRK fusion?
Yes. NTRK fusions have been found across many solid tumour types, which is why TRK inhibitors were approved as tumour-agnostic — the approval applies to the mutation, not the cancer type. The frequency varies widely. In secretory carcinoma and infantile fibrosarcoma, the rate is high. In the most common adult cancers such as lung and colorectal, it is rare. Dedicated biomarker testing is the only reliable way to know whether your tumour carries the fusion.
What kind of test is needed to detect an NTRK fusion?
RNA-based next-generation sequencing is the most reliable method, as it detects fusions directly. DNA-based NGS panels detect many fusions but can miss some. Immunohistochemistry is sometimes used as a first screening step but needs molecular confirmation. Testing is usually done on stored tissue from your original biopsy, so a repeat procedure is not always needed. Your oncologist or pathologist can advise on whether the result is sufficient to guide a treatment decision.
How long does TRK inhibitor treatment continue?
Treatment continues as long as it is working and you are tolerating it. There is no fixed number of cycles the way there is with some chemotherapy regimens. Response is assessed by scan every few months, and your oncologist will discuss continuing, adjusting, or changing treatment based on those results. If resistance develops, second-generation TRK inhibitors are used in some settings. Your oncologist will explain the plan if that becomes relevant.
Are TRK inhibitors available in India?
Availability in India has been increasing. Regulatory approval status and patient access programmes change over time, and your oncologist is the most reliable source of current information for your situation. Cost can be significant. Patient access programmes offered by manufacturers may reduce this, so ask your oncologist's team about eligibility before assuming the full out-of-pocket cost is the only option.
What if the NTRK fusion test comes back negative?
A negative result means no NTRK fusion was detected, and a TRK inhibitor is not indicated. Your oncologist will discuss other treatment options based on your cancer type, stage, and other biomarker results. A negative result on a good-quality RNA-based NGS test is generally definitive. If the initial test was DNA-based or limited in scope and there is clinical reason to look further, your oncologist may consider whether additional testing is warranted.
Does having an NTRK fusion mean chemotherapy is no longer needed?
Not necessarily. In some situations a TRK inhibitor is used as the primary treatment without chemotherapy. In others, particularly when the fusion is discovered after earlier treatments, it becomes an option if the cancer progresses. The sequencing depends on your cancer type, stage, and treatment history. Your oncologist will explain how the NTRK fusion result changes the plan — if at all — for your specific situation.