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Clinical outcomes in ALK-rearranged lung adenocarcinomas according to ALK fusion variants

 Yoon Jin Cha  ;  Hye Ryun Kim  ;  Hyo Sup Shim 
 Journal of Translational Medicine, Vol.14(1) : 296, 2016 
Journal Title
 Journal of Translational Medicine 
Issue Date
Adenocarcinoma/drug therapy ; Adenocarcinoma/enzymology* ; Adenocarcinoma/genetics* ; Adenocarcinoma/pathology ; Adult ; Aged ; Disease-Free Survival ; Female ; Gene Rearrangement/genetics* ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/drug therapy ; Lung Neoplasms/enzymology* ; Lung Neoplasms/genetics* ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Mutation/genetics* ; Oncogene Proteins, Fusion/metabolism* ; Pemetrexed/therapeutic use ; Proportional Hazards Models ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Pyrazoles/therapeutic use ; Pyridines/therapeutic use ; Pyrimidines/therapeutic use ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors ; Receptor Protein-Tyrosine Kinases/genetics* ; Sulfones/therapeutic use ; Treatment Outcome
Anaplastic lymphoma kinase ; Anaplastic lymphoma kinase inhibitor ; EML4-ALK fusion ; Non-small cell lung cancer ; Pemetrexed
BACKGROUND: Clinical outcomes of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer according to ALK fusion variants are not clear. We aimed to investigate the prevalence of ALK fusion variants and to compare clinical outcomes according to ALK fusion variants. METHODS: A retrospective analysis was conducted on patients with advanced ALK-rearranged adenocarcinoma treated with chemotherapy and ALK inhibitors. ALK rearrangement was identified by fluorescence in situ hybridization and confirmed by immunohistochemistry. Peptide nucleic acid-mediated quantitative polymerase chain reaction assays, designed to detect 28 types of echinoderm microtubule-associated protein-like 4 (EML)-ALK rearrangements, were performed. Clinicopathological analysis and treatment outcomes with platinum-based chemotherapy, pemetrexed therapy, and ALK inhibitors-including crizotinib and ceritinib-were evaluated. RESULTS: A total of 52 patients with ALK-rearranged lung adenocarcinoma were enrolled. EML4-ALK variant 1 (v1) was the most common variant (38.5 %) followed by the non-EML4 variant (36.5 %), EML4-ALK variant 3a/b (19.2 %), and EML4-ALK variant 2 (5.8 %). No clinicopathological distinction was found between the different ALK fusion variants. Treatment response rates for each therapeutic agent did not differ according to ALK fusion variant. However, EML4 variants, especially v1, showed significantly longer progression-free survival (PFS) on pemetrexed treatment than did non-EML4 variants (median 31.1 months versus 5.7 months, P = 0.003). PFS with platinum-based chemotherapy and ALK inhibitors did not differ according to ALK fusion variant. Multivariate survival analysis using Cox's regression model revealed v1 as the only predictive factor for prolonged PFS on pemetrexed. CONCLUSIONS: Among ALK fusion variants, v1 is the most common subtype. It showed superior progression-free survival on pemetrexed than did non-EML4 variants. No survival difference was demonstrated between variants treated with crizotinib or ceritinib.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Cha, Yoon Jin(차윤진) ORCID logo https://orcid.org/0000-0002-5967-4064
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