Effect of lorlatinib/lorlatinib on bone metastasis

Lorlatinib/Lorlatinib (Lorlatinib) is a highly potent, third-generation, oral tyrosine kinase inhibitor that inhibits anaplastic lymphoma kinase (ALK). In cell experiments, lorlatinib was shown to be more effective than second-generation inhibitors and had the broadest coverage of ALK resistance mutations. Despite resistance to previous ALK inhibitors (first-generation, second-generation, or both), lorlatinib has demonstrated potent antitumor activity, particularly intracranial activity in patients with central nervous system metastases, including leptomeningeal metastases.

Lung cancer is known to spread to other parts of the body. When lung cancer is diagnosed, approximately 20%-50% of patients with non-small cell lung cancer have metastasis. Common sites of distant metastasis are the brain (10%), bone (7%), and liver (5%). In addition to these organs, skeletal muscle is also one of the sites of metastasis of non-small cell lung cancer, and skeletal muscle metastases (SMM) mostly occur in the trunk or upper limbs.

Lorlatinib is administered as an oral tablet; no intravenous formulation is available. In a global phase 2 study, lorlatinib was shown to be effective in patients with EML4-ALK-positive lung cancer treated with previous-generation ALK inhibitors, such as alectinib or crizotinib. Clinical improvement was reported in 47% of patients who had previously received at least one ALK inhibitor, and their median PFS was 6.9 months. The median time to first tumor response was 1.4 months. Such rapid relief times and high response rates may be helpful for patients with painful SMM. However, these results still require more large-scale studies to confirm.