The good news
The Food and Drug Administration (FDA) approved larotrectinib (Vitrakvi) for adult and pediatric patients with NTRK gene fusion-positive solid tumors.
Why it’s important
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are implicated as drivers of cancer (oncogenic) development in various cancers including lung cancer. The prevalence of NTRK fusions is 0.1 to 0.3% in non-small cell lung cancer (NSCLC).
Larotrectinib is an oral TRK inhibitor that has received FDA approval based on the results of 3 clinical studies. LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431) trials included 339 pediatric and adult patients with an NTRK gene fusion cancer whose disease either progressed on standard treatment or they could not receive surgery for locally advanced disease.
The response rate for treatment with larotrectinib was 60% (complete response 24%) and control of cancer lasted for a median of more than 43 months. In 30 previously treated lung cancer patients, the response was 74%. The median progression-free survival (PFS) or time the cancer was controlled was 33 months. Larotrectinib had very good activity in the brain with many brain metastases responding to treatment. The most common side effects were rash, muscle pain, nausea, vomiting, fever, dizziness, weight gain, diarrhea, constipation, cough, fatigue, and abnormal laboratory tests.
What it means for patients
Larotrectinib is an effective treatment for NTRK fusion positive NSCLC. It is important to note that NTRK fusions are present in many tumors other than lung cancer – including thyroid, gastrointestinal, central nervous system, and salivary gland cancers as well as sarcomas and pediatric cancers. Although NTRK fusions are relatively uncommon, larotrectinib represents effective treatment for patients whose cancers contain this molecular abnormality. This supports the importance of doing biomarker (molecular, genomic) testing to evaluate newly diagnosed lung cancer patients and in patients whose cancer has not been previously tested for NTRK fusions.
What to look for
NTRK fusions represent another actionable target for cancer treatment. Look for more research attempting to identify novel targets to direct effective, personalized cancer therapy.