NTRK Fusion-Positive Cancers

Neurotrophic tyrosine receptor kinase (NTRK) Fusion-Positive Cancers are cases of cancer that have tested positive for a mutation in one of the NTRKs. NTRKs encode the TRK family of receptors, which are involved in cell signaling. The NTRK gene family includes NTRK1, NTRK2, and NTRK3.

Rearrangements in the NTRK genes can cause two genes to fuse together. When they produce the abnormal TRK proteins, that is when cancer cells can develop uncontrollably. There are nearly 5,000 cases of cancer every year that test positive for NTRK mutations.

NTRK mutations have been identified in the following cancer types:

• Breast cancer
• Non-small cell lung cancer
• Pancreatic cancer
• Cholangiocarcinoma
• Colorectal cancer
• Neuroendocrine cancer
• Thyroid cancer

How to Test for NTRK Gene Mutations

In order to confirm that a cancer patient is positive for the NTRK mutation, a biopsy of the tumor must be collected. It will be sent to a laboratory to be analyzed and tested using one of the following methods:

• Immunohistochemistry (IHC)
• Next-Generation Sequencing (NGS)
• Fluorescence in Situ Hybridization (FISH)
• Polymerase Chain Reaction (PCR)

The only way to become eligible for therapies targeting the NTRK gene fusions is to have a positive result from one of these tests, or another test for gene mutations.

NTRK Positive Cancer Treatment

The exact type of treatment patients with NTRK positive cancer receive can depend on the cancer type they have. However, many patients are eligible for targeted therapies once they have been tested for the NTRK mutation. Targeted therapies locate and disable abnormal cells and proteins to attack them. These therapies can be more effective because they are able to locate all of the cancerous cells while avoiding healthy cells, which causes less side effects than other types of treatment.

There are two drugs approved by the FDA for the treatment of NTRK positive cancers. They are larotrectinib (vitrakvi), approved in 2018, and entrectinib (rozlytrek), approved in 2019. According to two studies from MD Anderson and NCI, entrectinib shrank the tumors in 57% of trial participants while larotrectinib showed a response in 79% of trial participants. Although there are only two approved targeted therapies, there are many more clinical trials available for patients with NTRK positive cancer to enroll in with new and alternative treatment options. These trials provide early access to treatments for smaller groups of patients because in a few years, some of the drugs may be approved by the FDA and used commercially as the standard of care. Speak with your doctor if you are interested in learning more about enrolling in a clinical trial.