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Indications of Lorlatinib

Indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive in adults. This indication has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of ALK-positive or ROS-1-positive NSCLC.

Clinical guidelines generally recommend lorlatinib as a second- or third-line therapy for NSCLC patients who have received first-line treatment with an ALK inhibitor.

Approximately 3%–7% of NSCLC patients are ALK-positive; these patients are typically never-smokers or light smokers, relatively younger in age, and predominantly diagnosed with adenocarcinoma histologically.

ALK resistance mutations, gene amplification, activation of bypass signaling pathways, and progression of brain metastases (due to the low cerebrospinal fluid concentration of crizotinib) limit the long-term therapeutic efficacy of multiple ALK inhibitors (e.g., alectinib, ceritinib, crizotinib). As an ALK inhibitor capable of crossing the blood-brain barrier, lorlatinib demonstrates efficacy in patients with disease progression after treatment with other ALK inhibitors (including alectinib, ceritinib, crizotinib), which also includes the remission of central nervous system (CNS) lesions.

FDA,2021.03