From the Guidelines
Lorlatinib is a highly effective treatment option for central nervous system (CNS) tumors, particularly in patients with ALK-positive non-small cell lung cancer (NSCLC), due to its ability to cross the blood-brain barrier and demonstrate significant CNS penetration and activity against brain lesions 1. The association between CNS tumors and lorlatinib is strongly supported by recent studies, which have shown that lorlatinib can significantly reduce the risk of CNS progression in patients with brain metastases at baseline, with a 12-month cumulative incidence of CNS progression of 7% compared to 72% with crizotinib 1.
Key Benefits of Lorlatinib
- High CNS penetration and activity against brain lesions
- Significant reduction in risk of CNS progression
- Effective in patients with disease progression after treatment with other ALK inhibitors
- Can be used as subsequent therapy in patients with CNS metastases
Important Considerations
- Common side effects include hyperlipidemia, edema, increased weight, peripheral neuropathy, and cognitive effects 1
- Regular monitoring of lipid profiles, liver function, and cardiac function is recommended
- Dose adjustments may be necessary for patients experiencing severe adverse effects or those with hepatic impairment
- Patients should avoid grapefruit products and St. John's wort while taking lorlatinib, as these can affect drug metabolism
Clinical Implications
- Lorlatinib is a valuable treatment option for patients with ALK-positive CNS tumors, particularly those with brain metastases
- The medication's ability to cross the blood-brain barrier and demonstrate significant CNS penetration and activity against brain lesions makes it an effective choice for reducing the risk of CNS progression
- Clinicians should carefully monitor patients for common side effects and adjust treatment as necessary to minimize adverse effects and optimize outcomes 1.
From the Research
Association between CNS Tumors and Lorlatinib
- Lorlatinib is a potent, third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI) designed to penetrate the blood-brain barrier 2, 3, 4, 5, 6.
- Studies have shown that lorlatinib has substantial intracranial activity in patients with ALK-positive non-small-cell lung cancer (NSCLC), with or without baseline CNS metastases 2, 3, 4, 5, 6.
- The cumulative incidence of CNS progression was lower in patients treated with lorlatinib compared to those treated with crizotinib 2, 4, 5, 6.
- Lorlatinib was associated with a higher frequency of intracranial response compared to crizotinib, particularly in patients with measurable brain metastases 3, 4, 5, 6.
Efficacy of Lorlatinib in CNS Tumors
- Lorlatinib showed significant improvement in progression-free survival (PFS) compared to crizotinib in patients with advanced ALK-positive NSCLC, including those with CNS tumors 4, 5, 6.
- The 12-month PFS rate was higher in patients treated with lorlatinib compared to those treated with crizotinib, regardless of the presence of baseline CNS metastases 4, 5, 6.
- Lorlatinib also─served as an effective treatment option for patients with ALK-positive NSCLC who had progressed on crizotinib or second-generation ALK tyrosine kinase inhibitors 2, 3.
Safety of Lorlatinib in CNS Tumors
- The most common adverse events associated with lorlatinib were hyperlipidemia, edema, increased weight, peripheral neuropathy, and cognitive effects 3, 4, 5, 6.
- Grade 3 or 4 adverse events were more common in patients treated with lorlatinib compared to those treated with crizotinib, mainly due to altered lipid levels 4, 5, 6.
- However, the incidence of CNS adverse events was generally manageable, and most resolved without intervention or with lorlatinib dose modification 4.