title: Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer.
abstract: Mutational analysis was performed in the kinase domain (exons 18-21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p=0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p=0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness.
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, TaoYuan, Taiwan.
authors.forename: Meng-Heng
authors.initials: MH
authors.lastname: Hsieh
authors.forename: Yueh-Fu
authors.initials: YF
authors.lastname: Fang
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Chang
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
authors.forename: Shinn-Yn
authors.initials: SY
authors.lastname: Lin
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Liu
authors.forename: Chih-Lin
authors.initials: CL
authors.lastname: Liu
authors.forename: Hsiu-Chi
authors.initials: HC
authors.lastname: Chen
authors.forename: Yuan-Chieh
authors.initials: YC
authors.lastname: Ku
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chen
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chang
authors.forename: Ying-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Bae-Li
authors.initials: BL
authors.lastname: Hsi
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Tsai
authors.forename: Shiu-Feng
authors.initials: SF
authors.lastname: Huang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib