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Distinct clinical features and outcomes in never‐smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement
Author(s) -
Kim Hye Ryun,
Shim Hyo Sup,
Chung JinHaeng,
Lee Young Joo,
Hong Yun Kyoung,
Rha Sun Young,
Kim Se Hoon,
Ha SangJun,
Kim Se Kyu,
Chung Kyung Young,
Soo Ross,
Kim Joo Hang,
Cho Byoung Chul
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26311
Subject(s) - kras , anaplastic lymphoma kinase , medicine , lung cancer , crizotinib , cancer research , hazard ratio , ros1 , fluorescence in situ hybridization , oncology , epidermal growth factor receptor , tyrosine kinase , cancer , gene rearrangement , biology , confidence interval , gene , adenocarcinoma , genetics , receptor , colorectal cancer , malignant pleural effusion , chromosome
BACKGROUND: The objectives of this study were to determine the proportions of major oncogenic alterations and to examine survival in genotype‐specific subsets of never‐smokers with nonsmall cell lung cancer (NSCLC). METHODS: The authors concurrently analyzed mutations in the epidermal growth factor receptor ( EGFR ) and v‐Ki‐ ras 2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) genes and investigated anaplastic lymphoma kinase ( ALK ) gene rearrangements in samples from 229 never‐smokers with NSCLC. ALK rearrangements were identified by fluorescent in situ hybridization and were confirmed by immunohistochemistry. Mutations in EGFR (exons 18 to 21) and KRAS (codons 12 and 13) were determined by direct sequencing. RESULTS: Of 229 tumors, the frequency of EGFR mutations, ALK rearrangements, KRAS mutations, and no mutations (wild type [WT]) in any of the 3 genes ( WT/WT/WT ) was 48%, 8.3%, 3.5%, and 40.2%, respectively. All genetic alterations were mutually exclusive. The median progression‐free survival after treatment with EGFR tyrosine kinase inhibitors (TKIs) was 12.8 months, 6.3 months, 2.1 months, and 1.6 months in patients with EGFR mutations, the WT/WT/WT genotype, KRAS mutations, and ALK rearrangements, respectively. In a Cox regression model, the adjusted hazard ratio for the risk of disease progression after treatment with EGFR TKIs was 0.59 (95% confidence interval [CI], 0.40‐0.87; P = .008) for patients with EGFR mutations, 4.58 (95% CI, 2.07‐10.15; P < .001) for patients with ALK rearrangements, and 4.23 (95% CI, 1.65‐10.8; P = .003) for patients with KRAS mutations. Overall survival also differed significantly among genotypes. CONCLUSIONS: To the authors' knowledge, this was the largest comprehensive and concurrent analysis to date of 3 major oncogenic alterations in a cohort of East Asian never‐smokers with NSCLC. Because survival outcomes differed among genotypes, and drugs that target specific alterations currently are available, genetic profiling to identify genotype‐specific subsets can lead to successful treatment with appropriate kinase inhibitors. Cancer 2012;. © 2011 American Cancer Society.