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


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.


CONCLUSIONS
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.
Han
Sae-Won
SW
Department of Internal Medicine, Seoul National University Hospital, Seoul, 110-744 Korea.
Kim
Tae-You
TY
Hwang
Pil Gyu
PG
Jeong
Soohyun
S
Kim
Jeongmi
J
Choi
In Sil
IS
Oh
Do-Youn
DY
Kim
Jee Hyun
JH
Kim
Dong-Wan
DW
Chung
Doo Hyun
DH
Im
Seock-Ah
SA
Kim
Young Tae
YT
Lee
Jong Seok
JS
Heo
Dae Seog
DS
Bang
Yung-Jue
YJ
Kim
Noe Kyeong
NK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D016019:Survival Analysis
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib