What kind of lung cancer does lorlatinib/lorlatinib treat?

Lorlatinib is indicated for the treatment of adult patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) who have not previously received an ALK inhibitor or who have disease progression after treatment with alectinib or ceritinib or crizotinib and at least one other ALK inhibitor. Lorlatinibis an oral small moleculeALK and ROS1 kinase inhibitor that has been developed as a third-generation ALK-TKI to address drug resistance and improve brain penetration in patients with ALK-positive non-small cell lung cancer.

Non-small cell lung cancer accounts for 85% of lung cancer cases globally and remains a particularly difficult disease to treat. Gene rearrangement of anaplastic lymphoma kinase (ALK) is a genetic alteration that causes non-small cell lung cancer in many patients. Generally, ALK is a natural endogenous tyrosine kinase receptor that plays an important role in brain development and triggers activity on various specific neurons in the nervous system. Larlatinibhas the strongest clinical activity against multiple ALK resistance mutations and has demonstrated good efficacy in patients with known brain metastases.

Lorlatinib is effective in the treatment of patients with ALK-positive non-small cell lung cancer who have not received prior treatment or whose disease has worsened despite treatment with other ALK TKIs. Lorlatinib is also effective when the cancer has spread to the brain. Lorlatinibhas good oral bioavailability. In non-clinical studies of pharmacological inhibition of CYP3A4 by oral ritonavir, which also inhibits P-glycoprotein, these inhibitory interactions resulted in a 16-fold increase in absolute brain concentrations of lorlatinib without apparent toxicity, which may help optimize the clinical use of lorlatinib.