FDA Approves Larotrectinib for Advanced Cancers that Expresses TRK

Precision medicine took the spotlight again last week as the Federal Drug Administration (FDA) approved the drug larotrectinib (Vitrakvi(r)) developed by Bayer and Loxo Oncology.

According to the FDA, larotrectinib is approved for adults (pill form) and children (liquid form) for any advanced solid tumors “that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory alternative treatments or that have progressed following treatment.”

It is the first ever TRK inhibitor drug and the second FDA approved tumor agnostic cancer treatment; meaning the drug targets a common biomarker rather than tumor origin.

What is TRK

Tropomyosin Receptor Kinase (TRK) fusions are rare genetic abnormalities that occurs when one of the neurotrophic receptor tyrosine kinase (NTRK) genes (NTRK1, NTRK2, NTRK3) become connected to another gene that is not related (ETV6, LMNA, TPM3). This connection leads to TRK “signaling” that is uncontrolled and could lead to cancer. Only a small number of colon cancer patients present with this type of biomarker – about 1%.

NTRK gene fusions are identified using specific tests, most of which use next-generation sequencing (NGS). Other types of tests used include DNA fluorescence in situ hybridization (FISH) test and Immunohistochemistry (IHC) test, however, these testing types would require multiple testings to learn about the specifics of the NTRK genes and whether or not they are fused.

Unfortunately, not all patients are getting biomarker testing prior to their treatment decision making, therefore it is possible that the small subset of patients with this biomarker may be missed.


[bctt tweet=”It is important to ask your care team about biomarker testing to learn if you may have an NTRK gene fusion, or another biomarker which could affect your treatment options. @FightCRC https://fightcolorectalcancer.org/biomarked/” username=”@FightCRC”]

About the Study

The approval of larotrectinib is based on combined results from the Phase I adult trial, Phase II NAVIGATE trial, and Phase I/II pediatric SCOUT trial (N=55). Of the group, which consisted of 55 patients, four were colon cancer patients.

The results were amazing — larotrectinib reduced the size of tumors (overall response rate [ORR]) for approximately 75% of patients in the study, with only minimal side effects including nausea, fatigue, and anemia.

There are warnings of additional, more severe side effects, including neurotoxicity (damage to central and/or peripheral nervous system), hepatotoxicity (liver damage), and embryo-fetal toxicity.

While this is an exciting announcement, it’s important to remember that prior research suggests only 1% of all cancer patients present with TRK, therefore making this a small subset of the colorectal cancer population that will benefit from larotrectinib.

Who to Call for Help

Larotrectinib (Vitrakvi(R)) is available now, and there are programs in place to help patients access it.

  • The Vitrakvi Commitment Program(™) will refund the cost of the drug to payers, patients, and third party payers if the patient (who has tested positive for an NTRK gene fusion) does not get any benefit within 90 days of the start of the treatment.
  • The TRAK Assist(™) patient support program assists patients with reimbursement. To learn more, and for specifics on eligibility call 1-844-634-TRAK (8725)

Additional Resources

Learn more about cancer testing on our Dec 11 webinar: https://fightcolorectalcancer.org/events/tumor-vs-germline-testing-whats-the-difference-december-2018-webinar/

Biomarked: https://fightcolorectalcancer.org/biomarked/