Entretinib is an oral tyrosine kinase inhibitor that targets the fusion of ROS1 and NTRK genes. It is mainly used to treat ROS1 positive non-small cell lung cancer (NSCLC) and NTRK gene fusion positive solid tumors, with central nervous system permeability and effective control of brain metastases.

1. Basic information of the drug

(1) Drug category: Enqutinib belongs to the second-generation pan TRK/ROS1 tyrosine kinase inhibitors (TKIs) developed by Roche Pharmaceuticals.

(2) Approval time: First approved by the US FDA in August 2019, and approved for market in China in July 2022.

(3) Dosage specifications: Commonly available are 100mg and 200mg capsules, with a recommended daily oral dose of 600mg.

2 Indications for Treatment

(1) Main indications: Used for adult patients with ROS1 positive metastatic non-small cell lung cancer, as well as adult and pediatric patients with NTRK gene fusion positive solid tumors aged 12 and above.

(2) Special advantage: It shows significant therapeutic effect on brain metastases, with an objective response rate (ORR) of over 50%.

3 mechanisms of action

(1) Target action: Selective inhibition of TRKA/B/C, ROS1, and ALK kinase activity, blocking downstream signaling pathways.

(2) Treatment principle: Inducing tumor cell apoptosis by inhibiting the fusion protein of tropomyosin receptor kinase (TRK) and ROS1.

(3) Pharmaceutical characteristics: High blood-brain barrier penetration rate, cerebrospinal fluid concentration can reach 15-20% of plasma concentration.

4 Clinical efficacy

(1) Objective response rate: 57% in NTRK fused solid tumors and 77% in ROS1 positive NSCLC.

(2) Duration of remission: The median duration of remission (DOR) reached 24.6 months, significantly prolonging patient survival.

(3) Safety features: Common adverse reactions include dizziness, constipation, diarrhea, etc., mostly at level 1-2.