Major Research Findings

Lorlatinib is a powerful, brain-penetrating, third-generation anaplastic lymphoma kinase (ALK)/ROS proto-oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI) that is active against most known resistance mutations. 12 Lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. 2 It's also the first time that a tyrosine kinase inhibitor for lung cancer is associated with pulmonary arteriel hypertension. 9 The CROWN study showed that lorlatinib was more effective than crizotinib in patients with previously untreated ALK-positive advanced non-small cell lung cancer. 11 , 13 The study found that people who took lorlatinib were twice as likely to be alive with no tumor growth as those who took crizotinib after 1 year of treatment. 13

Reasons for Side Effects

Lorlatinib can cause side effects because ALK inhibitors affect normal cells as well as cancer cells. 16 This is due to the fact that the drug's mechanism of action targets tyrosine kinases, which are involved in cell signaling pathways that are important for both normal and cancerous cells. This can lead to unintended consequences in normal tissues. 16

Common Side Effects

Hyperlipidemia

One of the most common side effects of lorlatinib is hyperlipidemia, which can increase cholesterol and triglyceride levels. 8 , 7 , 4 , 13 , 2

Central Nervous System Side Effects

Lorlatinib can cause central nervous system side effects. These include dizziness, headache, drowsiness, cognitive impairment, and mood changes. 8 , 7 , 4 , 13 , 3 , 2

Weight Gain

Lorlatinib can cause weight gain. 8 , 7 , 4 , 13

Edema

Lorlatinib can cause edema. 8 , 7 , 4 , 13

Peripheral Neuropathy

Lorlatinib can cause peripheral neuropathy, which causes symptoms such as numbness and pain in the hands and feet. 8 , 7 , 4 , 13

Pulmonary Arterial Hypertension

Lorlatinib can cause pulmonary arterial hypertension. 9

Liver and Pancreatic Injury

Lorlatinib can cause liver and pancreatic injury. 5

Lung Toxicity

Lung toxicity is a potential fatal effect involving NSCLC patients exposed to TKIs. 10 In a systematic review, lung toxicity was reported in 105 of 4943 NSCLC patients (2.1%). 10 Brigatinib resulted as the most frequently involved in lung toxicity (7%). 10

Side Effects Countermeasures

Hyperlipidemia

Countermeasures for hyperlipidemia include diet and exercise therapy. Drug therapy such as cholesterol-lowering drugs is also considered as needed. 8 , 7 , 4

Central Nervous System Side Effects

Countermeasures for central nervous system side effects include drug therapy depending on the symptoms. 8 , 7 , 4 , 3

Weight Gain

Countermeasures for weight gain include diet and exercise therapy. 8 , 7 , 4

Edema

Countermeasures for edema include rest and wearing compression stockings. Drug therapy such as diuretics is also considered as needed. 8 , 7 , 4

Peripheral Neuropathy

Countermeasures for peripheral neuropathy include drug therapy and rehabilitation depending on the symptoms. 8 , 7 , 4

Comparison of Studies

Commonalities in Studies

Many studies have shown that lorlatinib is effective in treating ALK-positive non-small cell lung cancer. Additionally, it has been shown that lorlatinib has better brain penetration than conventional ALK inhibitors. 12 , 14 , 13 , 1

Differences in Studies

The frequency and severity of lorlatinib side effects vary depending on the study. For example, hyperlipidemia is reported more frequently in some studies than others. 7 , 4 , 13 , 1

Precautions for Real-Life Applications

Lorlatinib is an effective drug for treating ALK-positive non-small cell lung cancer, but it is important to remember that it can cause side effects. Consult with your doctor about the side effects before taking lorlatinib and take appropriate measures. 7 , 4

Limitations of Current Research

There is still not enough data on the long-term safety of lorlatinib. Also, effective preventive measures and treatments for lorlatinib side effects have not been fully established. 7 , 16 , 1

Future Research Directions

Research is needed to evaluate the long-term safety of lorlatinib and to develop effective preventive measures and treatments for lorlatinib side effects. 7 , 16 , 1

Conclusion

Lorlatinib is an effective drug for treating ALK-positive non-small cell lung cancer. However, lorlatinib can cause some side effects. Consult with your doctor about the side effects before taking lorlatinib and take appropriate measures. 7 , 16 , 1