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More than a 75% response rate when targeting NTRK fusion-positive tumors with larotrectinib

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Introduction

• The treatment of patients with NTRK fusion-positive cancers with a specific first-generation TRK inhibitor, such as larotrectinib or entrectinib, is associated with high response rates (>75%), regardless of tumor histology.

 

• NTRK gene fusions involving either NTRK1, NTRK2 or NTRK3 (encoding the neurotrophin receptors TRKA, TRKB and TRKC, respectively) are oncogenic drivers of various adult and pediatric tumor types.

 

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What are the TRK receptors

The Trk receptor family comprises three transmembrane 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 receptors tyrosine kinase (TK) are expressed in human neuronal tissue, and play an essential role in both the physiology of development and function of the nervous system.

 

NTRK fusion in cancer

In all reported Trk oncogenic gene fusions, the 3’ region of the NTRK gene is joined with a 5’ sequence of a fusion partner gene by an intrachromosomal or interchromosomal rearrangement, and the oncogenic chimaera is typically either constitutively activated or overexpressed.

 

NTRK gene fusion according tumor types?

Focus on two indications:

  • Pediatric cancer : 93% response rate

    Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. TRK fusions have a critical role in tumorigenesis in 40% of infant high-grade gliomas.
    Larotrectinib demonstrated a 93% response rate in pediatric patients with solid tumors with NTRK fusion

  • Thyroid cancer : 12% NTRK fusion positive

    Stage IV papillary thyroid carcinoma patients reach only 51% 5-year survival. Larotrectinib treatment yielded high response rates, including complete responses, in adolescents and adults with recurrent TRK fusion thyroid cancer. Responses with larotrectinib therapy were generally durable.

NTRK gene fusions as novel targets of cancer therapy across multiple tumor types

  • OncoDNA delivers the only available molecular profiling solution for NTRK 1, 2 and 3 through RNA-Seq
  • RNA-Seq is the best method to identify all kinds of fusions and to avoid the false negative risk that is inherent to DNA-based assays

How can I get the NTRK solution?

You have two possibilities to order a NTRK solution:

1) As a standalone
2) In addition to OncoDEEP (automatically included in NSCLC, glioblastoma & thyroïd cancer)

Ordering a solution is very simple: just log into OncoSHARE, and select your solution(s). If you don’t have a kit, we’ll send you one. After interpretation by our expert team an interactive report will be available for you on OncoSHARE. You can review, edit and/or share it.

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The case report

Alicia, 49 years old when diagnosed

Was given the OncoDEEP solution following a stage 3 lung cancer.

View Alicia's report