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Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib

Cited 641 time in Web of Science Cited 706 time in Scopus
Authors
Han, Sae-Won; Kim, Tae-You; Hwang, Pil Gyu; Jeong, Soohyun; Kim, Jeongmi; Choi, In Sil; Oh, Do-Youn; Kim, Jee Hyun; Kim, Dong-Wan; Chung, Doo Hyun; Im, Seock-Ah; Kim, Young Tae; Lee, Jong Seok; Heo, Dae Seog; Bang, Yung-Jue; Kim, Noe Kyeong
Issue Date
2005-04
Publisher
American Society of Clinical Oncology
Citation
Journal of Clinical Oncology, Vol.23 No.11, pp.2493-2501
Abstract
Purpose This study was undertaken to investigate the effects of epidermal growth factor receptor (EGFR) mutation and its downstream signaling on response and survival in non-small-cell lung cancer (NSCLC) patients treated with gefitinib. Patients and Methods For 90 consecutive NSCLC patients who had received gefitinib, EGFR mutation was analyzed by DNA sequencing of exons 18, 19, 21, and 23 in the EGFR tyrosine kinase domain. Expressions of phosphorylated (p) -Akt and p-Erk were determined via immunohistochemistry. Response rate, time to progression (TTP), and overall survival were compared between each group according to EGFR mutation, as well as p-Akt and p-Erk expression. Results Seventeen patients (18.9%; 95% CI, 10.8 to 27.0) harbored EGFR mutations. These mutations include deletions in exon 19 in seven patients, L858R in six patients, G719A in three patients, and a novel A859T in one patient. Response rate in patients with EGFR mutation was 64.7% (11 of 17 patients; 95% CI, 42.0 to 87.4), in contrast to 13.7% (10 of 73 patients; 95% CI, 5.8 to 21.6) in patients without mutation (P<.001). Moreover, these 17 patients with EGFR mutation had significantly prolonged TTP (21.7 v 1.8 months; P <.001) and overall survival (30.5 v 6.6 months; P <.001) compared with the remaining 73 patients without mutation. Although no significant correlation was detected between EGFR mutation and expressions of p-Akt or p-Erk, p-Akt overexpression was associated with prolonged TTP in patients with EGFR mutation. Conclusion Our data further support the importance of EGFR mutation with regard to gefitinib sensitivity. In addition to its predictive role, EGFR mutation confers significant survival benefits on NSCLC patients treated with gefitinib.
ISSN
0732-183X
Language
English
URI
http://hdl.handle.net/10371/9699
DOI
https://doi.org/10.1200/JCO.2005.01.388
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College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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