Lorlatinib/Lorlatinib: A rising star in the treatment of ALK-positive non-small cell lung cancer

Lorlatinib Lorlatinib is hailed as a new hope for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC). It is especially suitable for adult patients with advanced NSCLC who have not received ALK inhibitor treatment, or for patients whose disease has progressed after using other ALK inhibitors such as alectinib, ceritinib, and crizotinib. As an oral small molecule ALK and ROS1 kinase inhibitor, lorlatinib has been successfully developed as a third-generation ALK-TKI due to its excellent drug resistance and brain penetration ability.

Non-small cell lung cancer accounts for up to 85% of global lung cancer cases, and its treatment is extremely difficult. Gene rearrangement of anaplastic lymphoma kinase (ALK) is an important genetic change that causes non-small cell lung cancer in many patients. It is worth mentioning that ALK is a natural endogenous tyrosine kinase receptor that is critical to brain development under normal circumstances and plays an activating role on specific neurons in the nervous system. However, in lung cancer, lorlatinib has demonstrated strong clinical activity against multiple ALK resistance mutations, especially in patients with known brain metastases.

Lorlatinib brings new treatment opportunities to patients with ALK-positive non-small cell lung cancer who have not received treatment or whose disease has progressed despite receiving otherALK TKIs. In particular, lorlatinib has also shown to be effective when the cancer has spread to the brain. In addition, lorlatinib also has good oral bioavailability. Through interaction with drugs such as ritonavir, it can significantly increase the concentration of lorlatinib in the brain without obvious toxicity. This finding is expected to provide new ideas for optimizing the clinical application of lorlatinib.