Ceritinib/Ceritinib belongs to the first generation of targeted drugs

Ceritinib is a second-generation ALK inhibitor. The development of ALK inhibitors has gone through multiple stages, from the first-generation crizotinib, to the second-generation ceritinib, alectinib, and brigatinib, to the third-generation Lorlatinib. The development of each generation of drugs aims to overcome the resistance problems of the previous generation of drugs and improve the ability to control brain metastases.

The first-generation ALK inhibitor crizotinib has achieved significant efficacy in patients with ALK-positive non-small cell lung cancer (NSCLC). However, with the prolongation of treatment time, many patients will develop drug resistance, which is mainly caused by ALK gene mutations (such as L1196M, G1269A, etc.) or activation of bypass pathways (such as EGFR, c-MET signaling pathway). To overcome these drug resistance problems, second-generation ALK inhibitors emerged.

As a second-generation ALK inhibitor, ceritinib has higher inhibitory activity against crizotinib-resistant ALK mutations, especially mutations such as L1196M. In addition, ceritinib can better penetrate the blood-brain barrier and effectively treat patients with brain metastases, making it an important alternative to crizotinib after resistance. However, compared with other second-generation ALK inhibitors, ceritinib has stronger gastrointestinal side effects, so alectinib and brigatinib have gradually become more popular choices in clinical use.

The third generationALK inhibitor Lorlatinib (Lorlatinib) has further optimized the drug structure, not only targeting a wider range of ALK resistance mutations, but also more effectively entering the central nervous system, specifically used to solve the problem of patients with resistance to second-generation ALK inhibitors. Currently, lopotinib has been approved by the FDA for second-line and above treatment, and as a first-line treatment option in some cases.

Reference materials:https://www.novartis.com/our-products/pipeline/ceritinib