A pragmatic guide for management of adverse events associated with lorlatinib

Lung Cancer. 2024 May:191:107535. doi: 10.1016/j.lungcan.2024.107535. Epub 2024 Mar 15.

Abstract

Lorlatinib is a brain-penetrant, third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC). In clinical trials, lorlatinib has shown durable efficacy and a manageable safety profile in treatment-naive patients and in those who have experienced progression while receiving first- and/or second-generation ALK TKIs. Lorlatinib has a distinct safety profile from other ALK TKIs, including hyperlipidemia and central nervous system effects. Clinical trial data showed that most adverse events (AEs) can be managed effectively or reversed with dose modifications (such as dose interruptions or reductions) or with concomitant medications without compromising clinical efficacy or quality of life for patients. A pragmatic approach to managing AEs related to lorlatinib is required. We present patient-focused recommendations for the evaluation and management of select AEs associated with lorlatinib developed by clinicians and nurses with extensive lorlatinib expertise in routine clinical practice. The recommendations follow the general framework of "prepare, monitor, manage, reassess" to streamline AE management and assist in practical, actionable, and personalized patient care.

Keywords: Anaplastic lymphoma kinase; Carcinoma; Drug-related side effects and adverse reactions; Lorlatinib; Non-small cell lung cancer; Tyrosine kinase inhibitors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines* / adverse effects
  • Aminopyridines* / therapeutic use
  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Disease Management
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Lactams* / adverse effects
  • Lactams, Macrocyclic* / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyrazoles* / adverse effects
  • Pyrazoles* / therapeutic use

Substances

  • lorlatinib
  • Lactams
  • Aminopyridines
  • Pyrazoles
  • Protein Kinase Inhibitors
  • Lactams, Macrocyclic
  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents
  • ALK protein, human