NTRK and Lung Cancer

Support for this educational program provided by Amgen, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Genentech, Lilly Oncology, Merck, Novartis and Pfizer.

When tumor tissue is looked at under a microscope, physicians can see what type of cancer it is. But physicians can also look for changes in the DNA of the tumor that might be causing the tumor to grow. Sometimes these changes are called biomarkers or molecular markers.

One way to think about it is that our DNA is like an instruction manual. If there is a typo in the instruction manual, the cell receives wrong instructions and can grow into cancer. Biomarker testing looks for those typos, so physicians know if you are a candidate to receive a targeted therapy that directly addresses those typos. 

An error in the NTRK gene (pronounced en-track) is one biomarker that physicians look for in non-small cell lung cancer. If you have non-small cell lung cancer, it is important to talk to your doctor about comprehensive biomarker testing to see if you have an error in the NTRK gene or another biomarker. The results of this testing influence your treatment options. To learn more about biomarker testing, visit Lung.org/biomarker-testing. 

What is an NTRK gene fusion?

In a tumor with an NTRK gene fusion, a piece of the NTRK gene and a piece of an unrelated gene fuse, or join, together. This activates the NTRK gene in a way that causes uncontrolled cell growth and cancer.  NTRK gene fusions are present in many different types of cancer. Though NTRK gene fusions are rare in lung cancer (less than 1% of cases), there is an effective treatment for it, so it is very important to know if a patient has an NTRK gene fusion. 

Who is most likely to have an NTRK gene fusion?

There is no one type of patient who is most likely to have an NTRK gene fusion. 

What are the types of NTRK gene fusions?

There are three different types of NTRK genes called NTRK 1, 2 and 3.  The fusions are named by the two genes that are joined. So if you have an NTRK gene fusion, you might see the NTRK plus the name of the gene it fused with next to it listed on your report. In general, treatment is the same no matter which type of NTRK gene fusion you have. 

How do you know if you have an NTRK gene fusion?

NTRK gene fusions can be detected through next-generation sequencing (NGS). This type of testing places tissue from a patient’s tumor (gathered from a biopsy) in a machine that looks for a large number of possible biomarkers at one time. Not all NGS tests include NTRK so it is best to talk to your doctor to make sure you are getting the most comprehensive test you can. 

There may be some situations where a patient can’t undergo the biopsy needed to perform NGS, and so liquid biopsy may be recommended. A liquid biopsy can look for certain biomarkers in a patient’s blood. Talk to your doctor to make sure one of these tests was performed.  

Learn more about the different types of biomarker tests here.

What is the course of treatment like for someone with an NTRK gene fusion?

Knowing if you have an NTRK gene fusion is important no matter your stage of lung cancer but has the most treatment implications for stage four patients. 

Currently there are two approved targeted therapies for NTRK gene fusions in lung cancer: entrectinib and larotrectinib.  These drugs are given in pill form and directly target or inhibit the fusion that is making the cancer grow.

Typically, lung cancer patients are given entrectinib first because it can penetrate the brain and lung cancer often spreads to the brain. Within a few months to years, the cancer is likely to evolve, and the NTRK-inhibitor may stop working. Second-line treatment options for patients with NTRK gene fusions may include clinical trials, chemotherapy or chemotherapy plus immunotherapy. 

One important thing to note is that NTRK gene fusions are different than NTRK mutations. There are treatments available for NTRK fusions but not mutations.  However, if you have an NTRK fusion and then develop an NTRK mutation, it might mean you’ve developed a resistance mutation and the NTRK-inhibitor drugs might not work anymore. In that case, a clinical trial might be right for you. 

Work with your doctor to discuss your goals and options each time you have to make a treatment decision. The three big questions to ask are:

1. What is the goal of this treatment?
2. What are the potential side effects?
3. What other options do I have?

Research is happening at a rapid pace and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.