Consensus Recommendations for Management and Counseling of Adverse Events Associated With Lorlatinib: A Guide for
Mollie Reed1, Aimee-Lauren S Rosales2, Marc D Chioda3
1Tennessee Oncology, Sarah Cannon Research Institute, PLLC, Nashville, TN, USA.
Abstract:
Resistance to first- and second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) and development and progression of central nervous system metastases remain significant issues in the treatment of ALK-positive non-small-cell lung cancer. Lorlatinib is a novel third-generation ALK TKI that is able to penetrate the blood-brain barrier and has broad-spectrum potency against most known resistance mutations that can develop during treatment with crizotinib and second-generation ALK TKIs. The safety profile of lorlatinib is distinct from those of other ALK TKIs. Adverse events are typically mild to moderate in severity, seldom result in permanent discontinuations, and are generally manageable through lorlatinib dose modifications and/or standard medical therapy. This article provides guidance to advanced practice providers (e.g., nurses, nurse practitioners, physician assistants) and oncology pharmacists for the clinical management of key lorlatinib-emergent adverse reactions (i.e., hyperlipidemias, central nervous system effects, bodyweight increase, edema, and peripheral neuropathy). As lorlatinib is both a substrate and inducer of the CYP3A enzyme system and is contraindicated with strong CYP3A inducers, relevant drug-drug interactions are also highlighted.
Insights
Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), effectively treats ALK-positive non-small-cell lung cancer, including brain metastases. This guide helps manage its unique side effects and drug interactions for advanced practice providers and pharmacists.
Area of Science:
- Oncology
- Pharmacology
Background:
- Anaplastic lymphoma kinase (ALK) positive non-small-cell lung cancer (NSCLC) presents challenges with resistance to existing tyrosine kinase inhibitors (TKIs) and central nervous system (CNS) metastases.
- First- and second-generation ALK TKIs have limitations in overcoming resistance mutations and penetrating the blood-brain barrier.
Purpose of the Study:
- To provide clinical management guidance for lorlatinib, a third-generation ALK TKI, for advanced practice providers and oncology pharmacists.
- To address key lorlatinib-emergent adverse reactions and drug-drug interactions.
Main Methods:
- Review of lorlatinib's efficacy against resistance mutations and CNS penetration.
- Analysis of lorlatinib's distinct safety profile and common adverse events.
- Identification of drug-drug interactions, particularly with the CYP3A enzyme system.
Main Results:
- Lorlatinib demonstrates broad-spectrum potency against common ALK resistance mutations and penetrates the blood-brain barrier.
- Adverse events associated with lorlatinib are generally manageable with dose adjustments or standard therapies.
- Lorlatinib is a substrate and inducer of CYP3A, necessitating caution with strong CYP3A inducers.
Conclusions:
- Lorlatinib offers a valuable treatment option for ALK-positive NSCLC, including CNS metastases.
- Effective management of lorlatinib's adverse reactions and drug interactions is crucial for optimal patient outcomes.
- This guidance supports healthcare professionals in safely and effectively utilizing lorlatinib in clinical practice.
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