Summary

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• Lorlatinib (Lorbrena) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.
• Nine studies were reviewed to compare the safety and efficacy of lorlatinib to other ALK inhibitors in treating NSCLC.
• In terms of progression-free survival, lorlatinib shows superior results compared to crizotinib and closely follows alectinib and brigatinib; it also demonstrates remarkable benefits in controlling CNS progression among populations with baseline brain metastases.
• While comparisons involving overall survival improvements remain less conclusive for lorlatinib, alectinib has been shown to significantly improve OS compared to other ALK inhibitors like crizotinib.
• Adverse events associated with lorlatinib are noted as being among the highest when compared to other ALK inhibitors, including changes in lipid levels, weight gain, cognitive effects, and mood effects; however, its high efficacy, particularly in managing CNS involvement, distinguishes it from others.
• Alectinib emerges frequently as a preferred option due its balance between efficacy and safety, especially within the first-line or second-line settings, while brigatinib exhibits significant improvement in patient-reported outcomes.