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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
[Chinese Expert Consensus on Management of Special Adverse Effects Associated with Lorlatinib]
Qing Zhou1, Shun Lu2, Yong Li3
1Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Abstract:
Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), 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. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy. .
Insights
Lorlatinib, a third-generation ALK inhibitor, effectively treats advanced non-small cell lung cancer (NSCLC) with ALK fusions, even with resistance mutations. Patients require monitoring for manageable side effects like hyperlipidemia and CNS effects.
Area of Science:
- Oncology
- Pharmacology
Background:
- Anaplastic lymphoma kinase (ALK) fusions are a key driver in non-small cell lung cancer (NSCLC).
- Resistance to earlier ALK tyrosine kinase inhibitors (TKIs) necessitates novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy and safety of lorlatinib, a third-generation ALK TKI, in advanced ALK-positive NSCLC.
- To characterize the adverse event profile of lorlatinib, including CNS effects and hyperlipidemia.
Main Methods:
- Clinical assessment of lorlatinib's potency and brain penetration.
- Monitoring for a broad spectrum of resistance mutations.
- Evaluation of adverse drug reactions and patient management strategies.
Main Results:
- Lorlatinib demonstrates robust clinical activity against diverse ALK resistance mutations.
- Common adverse events include manageable hyperlipidemia and central nervous system effects.
- Lorlatinib exhibits significant brain-penetrant activity.
Conclusions:
- Lorlatinib is a potent therapeutic option for advanced ALK-positive NSCLC, including cases with resistance mutations.
- Careful patient monitoring and management are crucial for optimizing lorlatinib therapy.
- A multidisciplinary approach is recommended for comprehensive patient care.
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