Vitrakvi (Larotrectinib) for Cancer in Adults and Children

Uses, Side Effects, and Resistance

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Vitrakvi (larotrectinib) is a cancer drug that received Food and Drug Administration (FDA) accelerated approval for use with advanced solid tumors in children or adults with NTRK fusion proteins. It has been found to have both a high response rate and long-lasting benefits for many. Unlike many cancer medications that are designed for use with specific types of cancer, Vitrakvi may work across many different types.

A woman with cancer receiving her medicine

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Roughly 1 percent of solid tumors (but up to 60 percent of some tumors in children) contain a genetic change known as a neutrophin receptor kinase (NTRK) gene fusion. Larotrectinib is a selective tropomyosin receptor kinase (TRK) inhibitor that blocks the action of NTRK fusion proteins that lead to uncontrolled TRK signaling and tumor growth. In addition to the benefits, side effects are often mild relative to many other cancer treatments.


Vitrakvi is indicated for adults and children who have the NTRK gene fusion without a known acquired resistance mutation, who either have metastatic cancer or locally advanced cancer (for which surgery would be disfiguring), and for which no satisfactory alternative treatments exist (or if the cancer has progressed following these treatments).

Diagnosis of the gene fusion may be made on next-generation sequencing (see below). It is this specific genetic "fingerprint" that determines who may respond to the drug, which makes Vitrakvi a targeted therapy for cancer.

Types of Cancer

While an average of 1 percent of solid tumors contains NTRK fusion proteins, the incidence of the fusion gene may be as high as 60 percent or more in some rare tumor types, such as infantile fibrosarcoma and salivary gland tumors. While one percent may seem like a small number, the fusion gene has been found in a very wide range of tumor types, that represent a large number of people.

In the studies leading to approval, cancer types that were treated (and how many times they were treated) with larotrectinib included a variety of different tumors.

How Is It Used?

Vitrakvi is given twice daily, either as capsules or as an oral solution. The adult dose is 100 mg twice daily, and this is continued until a tumor progresses or side effects limit treatment.

Research Studies

Vitrakvi was approved as a result of three clinical trials in adults and children that demonstrated marked efficacy.

One study published in The New England Journal of Medicine looked at 55 adults and children ages 4 months to 76 years. In this study, the response rate was 75 percent (by an independent radiology review) and 80 percent according to the response investigator. It's not yet known how long the response will continue, as the median duration of response (the amount of time after which 50 percent of cancers would have progressed and 50 percent would still be controlled) was not reached at 8.3 months of follow-up.

The degree of response varied, with 13 percent complete responses, 62 percent partial responses, and 9 percent with stable disease. More than half of people remained progression-free after one year.

When the drug was first started, the median time before a response was evident was 1.8 months.

While responses such as these may not sound major to some, it's important to note how this differs from traditional treatments such as chemotherapy. With chemo, most people would take about 6 months to progress with cases of advanced cancer.

Pediatric Study

Another study published in Lancet Oncology looked at the effectiveness of larotrectinib in infants, children, and adolescents between the age of 1 month and 21 years, and found a 90 percent response rate in the children who had tumors with the fusion gene.

This was remarkable, as these children all had metastatic or locally advanced solid tumor or brain/spinal cord tumors that had either progressed, relapsed, or had not responded at all to currently available therapies.

Children who were treated but did not have the fusion gene had no objective response.

While most people studied had metastatic tumors, two of the children had non-metastatic but locally advanced infantile fibrosarcoma, in which conventional therapy would result in the loss of a limb. The tumors in these children shrunk enough that they were able to have limb-sparing surgery with curative intent, and remained free of cancer after 6 months of follow up.

There are several National Cancer Institute-supported clinical trials in progress further studying the drug and its effects on different types and stages of cancer.

How Genes Mutate

Targeted therapies are medications that target specific pathways or receptors that a cancer uses to grow. These therapies differ from chemotherapy drugs (drugs designed to eliminate any rapidly dividing cells) in that they specifically target cancer. For this reason, targeted therapies often have fewer side effects than chemotherapy.


Our DNA is made up of chromosomes, and on these chromosomes are thousands of genes. Genes can be thought of as a "code" that is used to create everything from eye color to proteins involved in the growth of cells.


In mutations, different "letters" may be inserted, deleted, or rearranged so that this code spells out an incorrect message for making a protein. In fusion genes, part of one gene is fused with another gene. There are two types of these genetic changes associated with cancer including:

  • inherited or germ-line mutations, which are abnormal genes that a person is born with. Some of these can predispose someone to the development of cancer. (An example is the BRCA gene mutations associated with breast cancer.)
  • acquired or somatic mutations, which are changes that occur after birth in reaction to environmental carcinogens, or simply due to the normal metabolic processes of cells. When genetic changes occur in the genes that code for proteins the control the growth of cancer cells (driver mutations), a cancer may develop.

Cancer Genes

Mutations in two types of genes can lead to the development of cancer (and often, genetic changes in both are present).

Two Types of Genes That Lead to Cancer

  1. Tumor Suppressor Genes
  2. Oncogenes

Tumor suppressor genes code for proteins that repair damaged DNA in cells, or eliminate the cell if it can't be repaired. When not repaired, these cells can go on to become cancer cells. Tumor suppressor genes are often autosomal recessive, meaning that both copies must be mutated or changed in order for the risk of cancer to occur. BRCA genes are examples of tumor suppressor genes.

Oncogenes are often autosomal dominant and are involved in the growth and division of cells. When these genes are abnormal, they can be visualized as controlling proteins to push down on the accelerator of a car (keeping a cell dividing) without ever stopping.

Mode of Action

While many targeted therapies target specific mutations in cancer cells (that subsequently code for abnormal proteins), Vitrakvi targets proteins that arise from a neurotrophic receptor tyrosine kinase (NTRK) gene fusion.

Tropomyosin receptor kinases (TRK) are a group of signaling proteins that are involved in the growth of cells. When the genes that make these proteins are abnormally fused to another gene, the proteins resulting from this fusion, can cause uncontrollable cellular growth.

Larotrectinib can inhibit these abnormal signals so that the cancer no longer grows. At the current time, larotrectinib is the only selective TRK inhibitor being studied.

Precision Medicine

Drugs such as Vitrakvi (larotrectinib) are an important component of what is called precision medicine. Precision medicine is an approach that looks at specific information about a person's tumor (such as the genetic changes discussed above) to diagnose and treat cancer. This is in contrast to the "one-size-fits-all" approach to treating cancers based on the type of cell alone.

The number of people with cancer who might benefit from precision medicine varies by tumor type, but it's estimated that all precision medicine therapies combined (including larotrectinib) may currently work in up to 40 percent to 50 percent of people overall.

Precision medicine treatment options are usually evaluated based on tumor type, but now this is changing. Keytruda (pembrolizumab) was the first precision medicine treatment used across cancer types, and now larotrectinib is the second.

Molecular Profiling

In order to know if someone with cancer might benefit from precision medicine, it's important to be aware of not only the type or subtype of cancer, but the underlying molecular and genetic changes that are present. For example, molecular testing (gene profiling) of lung cancers is now recommended for the majority of people who are diagnosed with the disease (anyone who has non-small cell lung cancer).

Next-Generation Sequencing

While tests for specific gene mutations may be done for specific cancers, detecting genetic changes in tumors such as the NTRK fusion gene requires next-generation sequencing. This testing is much more comprehensive and looks for mutations, gene amplification, and fusions (such as TRK fusions) that may be targetable by current drugs.

The NTRK fusion gene was found in the 1980s, but it was not until the availability of next-generation sequencing that scientists could test for the presence of this gene across different cancers.

Changes such as the NTRK fusion gene are referred to as "tumor agnostic" meaning that they may be found in many different types of cancer.

Side Effects

The side effects of cancer treatment are well known to many, especially those related to chemotherapy. Fortunately, side effects related to larotrectinib were relatively few and mild. Side effects are graded on a scale of 1 to 5, with 5 being the worst. In studies, 93 percent of patients had side effects classed as grade 1 or 2, 5 percent had grade 3 symptoms, and no grade 4 or 5 effects were noted.

Of even greater importance is that not a single person needed to discontinue to drugs due to side effects, and only 13 percent required a decrease in dose for this reason. Even when the dose was reduced for these people, however, the drug was no less effective.

The most common side effects included:

  • Anemia (17 to 22 percent)
  • Increased liver function tests (22 to 44 percent)
  • Weight gain (4 percent)
  • Lowered white blood cell count (21 percent)

In some patients, extreme nausea and ejection fraction decrease were found to be additional side effects experienced during the 28 days following the trial.

Acquired Resistance

Resistance is the reason why most cancers progress while on treatments such as targeted therapy, and 11 percent of the people studied developed resistance leading to disease progression.

It's thought that resistance is most often due to acquired mutations that alter NTRK, and hopefully (as we have seen with several other targeted therapies), second and third-generation drugs in this category will be developed for those who face resistance.


The cost of larotrectinib, like more recently approved cancer drugs, is substantial. It is difficult to price this drug especially since no other contemporary drug quite like it is available.

It is important to check with your healthcare provider to see what treatments are covered by your insurance.

A Word From Verywell

Vitrakvi (larotrectinib) is unique in that it can work for many different types of cancer to address the needs of a diverse population of people. It also appears to provide previously unseen effectiveness for some rare tumor types such as infant fibrosarcoma.

Precision medicine allows physicians to treat cancers based on molecular differences in the tumors, not just the cells seen under the microscope. Finally, for those who are frustrated at how long it takes for the research and development of new cancer drugs, larotrectinib is a prototype of a drug that has rapidly reached those who may benefit via breakthrough designation and accelerated approval.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

By Lynne Eldridge, MD
 Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."