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Anaplastic Lymphoma Kinase Translocation: A Predictive Biomarker of Pemetrexed in Patients with Non-small Cell Lung Cancer.
MedLine Citation:
PMID:  21642865     Owner:  NLM     Status:  Publisher    
INTRODUCTION:: This study compared the efficacy of pemetrexed in patients with anaplastic lymphoma kinase (ALK)-positive versus ALK-negative (epidermal growth factor receptor [EGFR] mutant or wild type [WT] for both ALK and EGFR) non-small cell lung cancer (NSCLC). METHODS:: Patients with advanced NSCLC who received second-line pemetrexed and beyond between March 2007 and April 2010 were screened for EGFR mutations and ALK rearrangements at Seoul National University Hospital. The clinical and in vitro efficacy of pemetrexed was evaluated for each genotypic group. RESULTS:: Ninety-five NSCLC patients were genotyped as follows: 43 (45%) EGFR mutation, 15 (16%) ALK translocation, and 37 (39%) WT. The overall response rate was superior in ALK-translocated patients compared with EGFR mutant or WT patients (46.7 versus 4.7 versus 16.2%, p = 0.001). ALK-positive patients showed longer time to progression than EGFR mutant or WT patients (9.2 versus 1.4 versus 2.9 months, p = 0.001). ALK positivity alone was a significant predictor for overall response rate (hazard ratio [HR] = 0.07, 95% confidence interval [CI]: 0.01-0.32; p = 0.001) and time to progression (HR = 0.44, 95% CI: 0.24-0.80; p = 0.007). ALK positivity remained independently significant regardless of treatment line (HR = 0.43, 95% CI: 0.24-0.77; p = 0.005). Thymidylate synthase mRNA levels in ALK-positive cells were significantly lower compared with control cells (p < 0.05). CONCLUSION:: Pemetrexed is an effective treatment in patients with ALK-positive NSCLC. ALK positivity was independently predictive of pemetrexed efficacy in NSCLC patients.
Jeong-Ok Lee; Tae Min Kim; Se-Hoon Lee; Dong-Wan Kim; Soyeon Kim; Yoon-Kyung Jeon; Doo Hyun Chung; Woo-Ho Kim; Young Tae Kim; Seok-Chul Yang; Young Whan Kim; Dae Seog Heo; Yung-Jue Bang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-2
Journal Detail:
Title:  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer     Volume:  -     ISSN:  1556-1380     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
*Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam; †Department of Internal Medicine, Seoul National University Hospital; ‡Cancer Research Institute, Seoul National University College of Medicine; and Departments of §Pathology and ∥Thoracic Surgery, Seoul National University Hospital, Seoul, Korea.
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