Lorlatinib for the treatment of patients with non-small cell lung cancer

T. Akamine, G. Toyokawa, Tetsuzo Tagawa, K. Yamazaki, T. Seto, S. Takeo, Masaki Mori

Research output: Contribution to journalArticle

Abstract

Lorlatinib is a novel third-generation tyrosine kinase inhibitor (TKI) which targets anaplastic lymphoma kinase (ALK) as well as receptor tyrosine kinase c-ros oncogene 1 (ROS1). A critical limitation of conventional ALK/ROS TKIs is their association with acquired resistance mutations (particularly ALK G1202R and ROS1 G2032R) in the ALK or ROS1 gene, although these are not the only resistance mechanisms. Another limitation of this class of drugs is their inadequate efficacy against central nervous system metastasis, likely attributable to the blood–brain barrier (BBB). Therefore, lorlatinib was developed to overcome these limitations by being more potent, selective and permeable to the BBB than previous-generation ALK/ROS1 TKIs and subsequently received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) in April 2017. In September 2018, Japan became the first country where lorlatinib received approval for treating patients with ALK-rearranged non-small cell lung cancer. Eventually, the FDA approved lorlatinib (Lorbrena; Pfizer) in November 2018. Lorlatinib use is expected to increase in importance, owing to its promising efficacy in clinical trials.

Original languageEnglish
Pages (from-to)107-116
Number of pages10
JournalDrugs of Today
Volume55
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

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Non-Small Cell Lung Carcinoma
Oncogenes
United States Food and Drug Administration
Therapeutics
Receptor Protein-Tyrosine Kinases
Protein-Tyrosine Kinases
7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo(4,3-h)(2,5,11)benzoxadiazacyclotetradecine-3-carbonitrile
anaplastic lymphoma kinase
Japan
Central Nervous System
Clinical Trials
Neoplasm Metastasis
Mutation
Pharmaceutical Preparations
Genes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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Lorlatinib for the treatment of patients with non-small cell lung cancer. / Akamine, T.; Toyokawa, G.; Tagawa, Tetsuzo; Yamazaki, K.; Seto, T.; Takeo, S.; Mori, Masaki.

In: Drugs of Today, Vol. 55, No. 2, 01.02.2019, p. 107-116.

Research output: Contribution to journalArticle

Akamine, T. ; Toyokawa, G. ; Tagawa, Tetsuzo ; Yamazaki, K. ; Seto, T. ; Takeo, S. ; Mori, Masaki. / Lorlatinib for the treatment of patients with non-small cell lung cancer. In: Drugs of Today. 2019 ; Vol. 55, No. 2. pp. 107-116.
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