Abstract
Lung cancer remains the leading cause of cancer deaths in the world with 1.69 million deaths in 2015. A total of 85% of lung cancer cases are non-small-cell lung cancers (NSCLCs). Driver mutations associated with anaplastic lymphoma kinase (ALK) have been identified in a variety of malignancies, including NSCLC. An ALK inhibitor (crizotinib, ceritinib and alectinib) is the preferred therapeutic approach to those advanced ALK fusion variant-positive NSCLC patients. Brigatinib, a next-generation ALK inhibitor, shows promising activity in ALK-rearranged NSCLC that have previously received crizotinib with response rates in ALTA ranging from 42-50%, intracranial response 42-67% and median progression-free survival 9.2-12.9 months. Randomized Phase III trial, ALTA-1 L is investigating brigatinib in ALK inhibitor-naive patients.
Keywords:
ALK; ALTA; EML4–ALK rearrangement; NSCLC; alectinib; brigatinib; central nervous system metastases; ceritinib; crizotinib; lung cancer.
Publication types
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Clinical Trial, Phase III
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Randomized Controlled Trial
MeSH terms
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Adult
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Aged
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Anaplastic Lymphoma Kinase
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / pathology
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Central Nervous System Neoplasms / drug therapy*
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Central Nervous System Neoplasms / genetics
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Central Nervous System Neoplasms / pathology
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Crizotinib
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Disease-Free Survival
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Drug Resistance, Neoplasm / drug effects
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Male
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Middle Aged
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Mutation
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Neoplasm Proteins / genetics
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Oncogene Proteins, Fusion / genetics
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Organophosphorus Compounds / administration & dosage*
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Organophosphorus Compounds / adverse effects
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Pyrazoles / administration & dosage
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Pyrazoles / adverse effects
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Pyridines / administration & dosage
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Pyridines / adverse effects
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Pyrimidines / administration & dosage*
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Pyrimidines / adverse effects
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptor Protein-Tyrosine Kinases / genetics*
Substances
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Neoplasm Proteins
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Oncogene Proteins, Fusion
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Organophosphorus Compounds
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Pyrazoles
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Pyridines
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Pyrimidines
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Crizotinib
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ALK protein, human
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Anaplastic Lymphoma Kinase
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Receptor Protein-Tyrosine Kinases
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brigatinib