Complex mutation patterns of epidermal growth factor receptor gene associated with variable responses to gefitinib treatment in patients with non-small cell lung cancer.
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.
Hsieh
Meng-Heng
MH
Department of Thoracic Medicine, Chang Gung Memorial Hospital, TaoYuan, Taiwan.
Fang
Yueh-Fu
YF
Chang
Wen-Cheng
WC
Kuo
Han-Pin
HP
Lin
Shinn-Yn
SY
Liu
Hui-Ping
HP
Liu
Chih-Lin
CL
Chen
Hsiu-Chi
HC
Ku
Yuan-Chieh
YC
Chen
Ya-Ting
YT
Chang
Ya-Hui
YH
Chen
Ying-Tsong
YT
Hsi
Bae-Li
BL
Tsai
Shih-Feng
SF
Huang
Shiu-Feng
SF
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*
D000970:Antineoplastic Agents; D017931:DNA Primers; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib