New Drug Approved for Patients with Rare Gene Fusion

By Sara Rothschild, MPH, Vice President, Program Services & Jerry Call, Data Analyst

The Food and Drug Administration granted accelerated approval on November 26th to larotrectinib (VITRAKVI) for adult and pediatric patients with 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.

What is an NTRK fusion?

The Trk receptor family comprises three proteins referred to as Trk A, B and C (TrkA, TrkB and TrkC) receptors, and are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. These receptor tyrosine kinases (TK) are expressed in human neuronal tissue and play an essential role in both the physiology of development and function of the nervous system through activation by neurotrophins (NTs). When an NTRK fusion occurs, a portion of a gene gets swapped with another gene (whether the same chromosome or different chromosomes). These fusions are reported in cancers, with the most common being salivary gland tumors, soft tissue sarcoma, infantile fibrosarcoma, and thyroid cancer.

How is this important to GIST?
Who should get tested?

Although these mutations are rare, the response rate to larotrectinib is very high (75 percent overall response rate across different types of solid tumors). This makes testing extremely important. In patients where no mutation was found after basic mutational testing (KIT and PDGFRA mutation testing), advanced testing should be performed and should test for a number of different mutations as well as SDHB staining (IHC). Advanced testing is most efficiently done with testing panels that test for many different mutations at one time including NTRK fusion mutations. Laboratories that have panels that have been specifically designed to include the rare mutations that occur in GIST include Knight Diagnostic Laboratories and Foundation Medicine (there may be others as well). For patients with previous negative testing (no mutation found) in multiple genes, they should check to ensure that NTRK fusions were included in that testing and if not, should be retested for NTRK fusion mutations. Dr. Jason Sicklick, a GIST specialist currently with Moores Cancer Center, University of California, San Diego, presented data several years ago, in a webinar for the LRG, from a project he did in collaboration with Foundation Medicine and observed that patients with these fusions typically range in age between 30-50s. His data also showed that the fusions are more common in men than women and that the tumors can occur anywhere in GI tract. Additionally, one-third of tumors are associated with lymph metastases and 40% are associated with distant metastatic disease.


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Patient Assistance

The Vitrakvi Commitment Program is managed by Bayer Oncology. NTRK gene fusion positive patients will pay for VITRAKVI only if they receive a clinical benefit from VITRAKVI. Full or partial refunds (for up to 60 days) will be issued to patients and the primary payer when lack of a clinical benefit occurs. To learn more about support through TRAK Assist, call 1-844-634-8725 or visit