Sustained Improvement in the Management of Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocation: Where Are We Running?
ALK
ALK inhibitors
NSCLC
alectinib
brain metastases
brigatinib
ceritinib
ensartinib
lorlatinib
resistance mechanisms
Journal
Current oncology (Toronto, Ont.)
ISSN: 1718-7729
Titre abrégé: Curr Oncol
Pays: Switzerland
ID NLM: 9502503
Informations de publication
Date de publication:
16 05 2023
16 05 2023
Historique:
received:
21
03
2023
revised:
06
05
2023
accepted:
08
05
2023
medline:
29
5
2023
pubmed:
26
5
2023
entrez:
26
5
2023
Statut:
epublish
Résumé
ALK translocation amounts to around 3-7% of all NSCLCs. The clinical features of ALK+ NSCLC are an adenocarcinoma histology, younger age, limited smoking history, and brain metastases. The activity of chemotherapy and immunotherapy is modest in ALK+ disease. Several randomized trials have proven that ALK inhibitors (ALK-Is) have greater efficacy with respect to platinum-based chemotherapy and that second/third generation ALK-Is are better than crizotinib in terms of improvements in median progression-free survival and brain metastases management. Unfortunately, most patients develop acquired resistance to ALK-Is that is mediated by on- and off-target mechanisms. Translational and clinical research are continuing to develop new drugs and/or combinations in order to raise the bar and further improve the results attained up to now. This review summarizes first-line randomized clinical trials of several ALK-Is and the management of brain metastases with a focus on ALK-I resistance mechanisms. The last section addresses future developments and challenges.
Identifiants
pubmed: 37232842
pii: curroncol30050384
doi: 10.3390/curroncol30050384
pmc: PMC10217667
doi:
Substances chimiques
Anaplastic Lymphoma Kinase
EC 2.7.10.1
Protein Kinase Inhibitors
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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