Entrectinib: A Review in NTRK plus Solid Tumours and ROS1+ NSCLC

Entrectinib (Rozlytrek(R)) is an orally active, CNS-penetrant, small-molecule, selective inhibitor of the tropomyosin receptor tyrosine kinases TRKA/B/C [encoded by the neurotrophic tyrosine receptor kinase (NTRK) genes NTRK1/2/3, respectively], the proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and the anaplastic lymphoma kinase gene (ALK). It is approved for the treatment of adults and paediatric patients aged >= 12 years with NTRK fusion-positive (NTRK+) solid tumours and adults with ROS1 fusion-positive (ROS1+) non-small-cell lung cancer (NSCLC). In trials in adults, entrectinib induced clinically meaningful and durable systemic responses in tyrosine kinase inhibitor (TKI)-naive patients with locally-advanced or metastatic NTRK+ solid tumours or ROS1+ NSCLC, irrespective of the presence or absence of CNS metastases at baseline. Moreover, entrectinib demonstrated substantial intracranial efficacy in patients with baseline CNS metastases. Entrectinb efficacy in paediatric patients was established on the basis of extrapolation of clinical trial data from adults with NTRK+ solid tumours and children and adolescents aged < 21 years with recurrent or refractory NTRK+ CNS/solid tumours. Entrectinib was generally well tolerated, with a manageable safety profile. Thus, entrectinib expands the range of treatment options for advanced NTRK+ solid tumours and ROS1+ NSCLC, and may be of particular value in patients with existing CNS metastases and those who are at risk of developing CNS metastases.

Automated summary

Entrectinib is an orally active small-molecule inhibitor targeting TRK and ROS1 genes, showing significant efficacy in treating NTRK+ solid tumors and ROS1+ NSCLC, including patients with CNS metastases. Its efficacy in pediatric patients is based on extrapolation from adult clinical trial data, with generally good tolerability and safety profile.