What targeted drugs should be taken after resistance to Crizotinib?

Since the introduction of crizotinib (Crizotinib) into clinical practice, the vast majority of patients will relapse due to drug resistance. Currently a variety of otherALK inhibitors have been developed. These inhibitors are more effective than crizotinib and can overcome gatekeepersL1196M mutations, etc., depending on the specific inhibitor. Next generationALK tkis have made significant progress in overcoming some of the limitations of crizotinib, particularly efficacy and central nervous system penetration.

New generationALK inhibitors are generally effective in crizotinib-resistant patients, with ORRs in clinical studies ranging from 48% to 71%, and median PFS ranging from 6.9 to 13.4 months. The FDA has approved the next-generation ALK inhibitors ceritinib and alectinib for use after progression on crizotinib. With these improvements, the distribution of resistance mechanisms is expected to change. Biopsies of these next-generation drugs have shown a narrower range of resistance mutations, with enrichment of certain mutations such as ALK G1202R. Since only lorlatinib has demonstrated efficacy against all clinically identified resistance mutations, appropriate sequencing of TKIs needs to be case-by-case and based on the mutations detected.

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 per box may be around RMB 15,000. The price of the original Turkish version of Crizotinib sold overseas may be more than RMB 10,000 per box (the price may fluctuate due to exchange rates), which is expensive. There are also cheaper generic crizotinib drugs available overseas. The ingredients are basically similar to those of the original drugs sold domestically and abroad. For example, the price of 250mg*60 tablets produced by a Bangladesh pharmaceutical factory may be more than 2,000 yuan per box (the price may fluctuate due to exchange rates).