Which generation of targeted drug is brigatinib? What are its unique advantages compared with other targeted drugs?

Brigatinib, also known as brigatinib, is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), mainly used to treat ALK-positive non-small cell lung cancer (NSCLC). As a new generation of ALK inhibitors, brigatinib not only has advantages in overcoming drug resistance, but also shows stronger efficacy and longer lasting effects.

ALKTargeted drugs can be divided into first generation (crizotinib), second generation (alectinib, ceritinib, brigatinib) and third generation (lorlatinib) based on development time and mechanism of action. Although brigatinib is classified as a second-generation drug in some literature, some studies also regard it as a third-generation drug due to its strong ability to inhibit drug-resistant mutations. Its main mechanism of action is to irreversibly inhibit ALKkinase activity, including high sensitivity to crizotinib-resistant mutations (such as L1196M) making it an effective option for ALK positive lung cancer patients.

The advantages of brigatinib are mainly reflected in its stronger ability to suppress drug-resistant mutations, better brain penetration, and longer progression-free survival (PFS). In clinical trials, brigatinib significantly extended patients' progression-free survival and reduced the risk of disease progression compared with crizotinib. In addition, it can effectively penetrate the blood-brain barrier (BBB) and has a good control effect on patients with brain metastasis, which happens to be one of the common metastasis sites in patients with ALK positive lung cancer.

SomeALK positive patients will develop drug resistance after taking drugs such as crizotinib and alectinib for a period of time, and brigatinib has shown a good inhibitory effect on a variety of drug-resistant mutations. In particular, mutations such as L1196M and G1202R often lead to the failure of first-generation and some second-generation ALK inhibitors. However, brigatinib can still maintain high inhibitory activity, making it an important choice for patients with drug resistance.

Reference materials:https://www.alunbrig.com/