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 language | English |
|---|---|
| Pages (from-to) | 107-116 |
| Number of pages | 10 |
| Journal | Drugs of Today |
| Volume | 55 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2019 |
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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 journal › Article
}
TY - JOUR
T1 - Lorlatinib for the treatment of patients with non-small cell lung cancer
AU - Akamine, T.
AU - Toyokawa, G.
AU - Tagawa, Tetsuzo
AU - Yamazaki, K.
AU - Seto, T.
AU - Takeo, S.
AU - Mori, Masaki
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
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U2 - 10.1358/dot.2019.55.2.2927983
DO - 10.1358/dot.2019.55.2.2927983
M3 - Article
VL - 55
SP - 107
EP - 116
JO - Drugs of Today
JF - Drugs of Today
SN - 0025-7656
IS - 2
ER -