Which generation of targeted drugs does lorlatinib belong to and its indications?

Lorlatinib is a third-generation ALK (anaplastic lymphoma kinase)-targeted drug specifically developed for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Compared with the first-generation crizotinib (Crizotinib) and the second-generation alectinib (Alectinib), brigatinib (Brigat inib) and other drugs, lorlatinib has stronger ALK inhibitory activity, especially maintaining good inhibitory effect against multiple drug-resistant mutations (such as G1202R). At the same time, it also has excellent central nervous system (CNS) penetrating ability and can effectively control or delay brain metastasis. It is one of the important choices for late-line or even first-line treatment of ALK-positive patients.

The main indication of lorlatinib isALK positive metastatic non-small cell lung cancer (NSCLC). Among the approved labels in China and other countries, lorlatinib is indicated for:

1.Patients whose disease progresses despite treatment with crizotinib and at least one otherALK TKI;

2.Or patients who have progressed after receiving alectinib or brigatinib as first-line treatment;

3.In some regions, such as the United StatesFDA, it is also approved for first-line treatment of untreated ALKpositive NSCLC patients.

In addition toALKpositive, lorlatinib can also inhibit someROS1positiveNSCLC, but the use of this indication needs to be approved by local regulatory agencies.

Clinical studies have shown that lorlatinib is effective in the treatment ofALKpositive advanced stageNSCLCIt has a high objective response rate (ORR) among patients, and its control effect on brain metastases is particularly outstanding. In patients who have previously used ALK inhibitors, lorlatinib can still play a role and is one of the few targeted drugs that is still active against multi-drug resistance mutations. Studies of its first-line treatment (such as the CROWN trial) have shown more durable progression-free survival than alectinib, making its status increasingly prominent in global treatment guidelines.

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

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