Common metastatic sites after Crizotinib resistance

Patients with ALK+ NSCLC most commonly present with advanced disease involving multiple sites, particularly lymph nodes, pleural and pericardial surfaces, brain, and liver, and despite significant and often durable responses, the vast majority of patients treated with crizotinib will experience disease progression. Crizotinib is an oral small molecule ATP competitive inhibitor originally developed as a cMET kinase inhibitor and subsequently found to inhibit ALK and ROS1 kinases in biochemical characterization.

After resistance to crizotinib, common metastasis sites include the meninges, adrenal glands, bones, lungs, liver and digestive tract. The occurrence of drug resistance may be related to the patient's insufficient dosage of ALK inhibitors, drug penetration barriers, and low effective drug concentrations in tumor tissues. It may also be caused by multiple drug resistance mechanisms inside and outside tumor cells. There were initially significant and durable responses to crizotinib. If a patient develops drug resistance after taking crizotinib, he or she should inform the doctor in time and adjust the drug use under the guidance of the doctor.

The original drug crizotinib has been launched in China and is covered by medical insurance, but it is only reimbursed for patients who meet the indications. The price of each box may be around 15,000 yuan. The price of the Turkish original version of crizotinib sold overseas may be more than 10,000 yuan per box (the price may fluctuate due to exchange rates), which is expensive. There are already cheaper generic crizotinib drugs overseas. The ingredients are basically similar to the original drugs sold domestically and abroad. For example, the price of a box of 250mg*60 tablets produced by a Bangladeshi pharmaceutical factory may be more than 2,000 yuan (the price may fluctuate due to exchange rates).