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Update on Lorlatinib: Role in Reducing the Risk of Disease Progression in ALK-Positive NSCLC

Karen M Yun1, Lyudmila A Bazhenova1

  • 1Department of Hematology-Oncology, Moores Cancer Center at UC San Diego Health, La Jolla, CA, USA.

Cancer Management and Research
|March 7, 2022
PubMed

Insights

Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, shows superior efficacy in advanced ALK-positive non-small cell lung cancer (NSCLC). It is effective against resistance mutations and in the brain, offering a new option for patients.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Lorlatinib is an oral third-generation anaplastic lymphoma kinase (ALK) inhibitor.
  • It demonstrates activity in advanced ALK-positive non-small cell lung cancer (NSCLC).
  • The phase 3 CROWN trial showed superior efficacy of lorlatinib over crizotinib in treatment-naïve patients.

Purpose of the Study:

  • To provide an overview of lorlatinib's efficacy and safety.
  • To discuss lorlatinib's position in the therapeutic approach for advanced ALK-positive NSCLC.
  • To compare lorlatinib with other ALK inhibitors, acknowledging the lack of direct head-to-head studies with second-generation inhibitors.

Main Methods:

  • Review of clinical trial data, including the CROWN trial.
  • Analysis of lorlatinib's efficacy in systemic and intracranial settings.
  • Evaluation of lorlatinib's activity against ALK resistance mutations.

Main Results:

  • Lorlatinib demonstrated superior systemic and intracranial efficacy compared to crizotinib in treatment-naïve patients.
  • Lorlatinib retains anti-tumor effects against various ALK resistance mutations.
  • Several ALK inhibitors, including lorlatinib, are approved for advanced ALK-positive NSCLC.

Conclusions:

  • Lorlatinib is a valuable therapeutic option for advanced ALK-positive NSCLC.
  • Its efficacy against resistance mutations and in the central nervous system is notable.
  • Further evaluation is needed to define its optimal role relative to second-generation ALK inhibitors.
Keywords:
anaplastic lymphoma kinaselorlatinibnon-small cell lung cancer

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