Efficacy and safety of NTRK inhibitors in patients with NTRK fusion-positive lung and thyroid cancers.
David S HongAlexander DrilonLori J WirthPublished in: Clinical advances in hematology & oncology : H&O (2024)
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are implicated in various cancers, including those of the lung and thyroid. The prevalence of NTRK fusions is 0.1 to 0.3% in non-small cell lung cancer (NSCLC) and as high as 26% in pediatric papillary thyroid carcinoma. Detection methods include immunohistochemistry, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, and next-generation sequencing. Management of NTRK fusion-positive lung cancer primarily involves targeted therapies, notably the tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib. Both agents demonstrate high response rates and durable disease control, particularly in metastatic adenocarcinoma of the lung. They are preferred as first-line treatments because of their efficacy over immunotherapy. Possible adverse events include dizziness, weight gain, neuropathy-like pain, and liver enzyme elevation. Larotrectinib and entrectinib also produce robust and durable responses in NTRK fusion-positive thyroid cancer that is refractory to radioactive iodine. Second-generation TRK inhibitors that have been designed to overcome acquired resistance are under investigation.
Keyphrases
- weight gain
- small cell lung cancer
- squamous cell carcinoma
- body mass index
- copy number
- lymph node
- chronic pain
- risk factors
- tyrosine kinase
- pain management
- gene expression
- genome wide
- weight loss
- magnetic resonance imaging
- young adults
- physical activity
- real time pcr
- locally advanced
- childhood cancer
- preterm birth
- sensitive detection
- quantum dots