Epidermal growth factor receptor mutation detection using high-resolution melting analysis predicts outcomes in patients with advanced non small cell lung cancer treated with gefitinib.
OBJECTIVE
Epidermal growth factor receptor (EGFR) mutations, especially deletional mutations in exon 19 (DEL) and L858R, predict gefitinib sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we validated EGFR mutation detection using high-resolution melting analysis (HRMA) and evaluated the associations between EGFR mutations and clinical outcomes in advanced NSCLC patients treated with gefitinib on a larger scale.


METHODS
The presence of DEL or L858R was evaluated using HRMA and paraffin-embedded tissues and/or cytologic slides from 212 patients. In 66 patients, the results were compared with direct sequencing data.


RESULTS
HRMA using formalin-fixed tissues had a 92% sensitivity and a 100% specificity. The analysis was successfully completed in 207 patients, and DEL or L858R mutations were detected in 85 (41%) patients. The response rate (78% versus 8%), time-to-progression (median, 9.2 versus 1.6 months), and overall survival (median, 21.7 versus 8.7 months) were significantly better in patients with EGFR mutations (P < 0.001). Even among the 34 patients with stable diseases, the time-to-progression was significantly longer in patients with EGFR mutations. Patients with DEL (n = 49) tended to have better outcomes than those with L858R (n = 36); the response rates were 86% and 67%, respectively (P = 0.037), and the median time-to-progression was 10.5 and 7.4 months, respectively (P = 0.11).


CONCLUSIONS
HRMA is a precise method for detecting DEL and L858R mutations and is useful for predicting clinical outcomes in patients with advanced NSCLC treated with gefitinib.
Takano
Toshimi
T
Division of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Ohe
Yuichiro
Y
Tsuta
Koji
K
Fukui
Tomoya
T
Sakamoto
Hiromi
H
Yoshida
Teruhiko
T
Tateishi
Ukihide
U
Nokihara
Hiroshi
H
Yamamoto
Noboru
N
Sekine
Ikuo
I
Kunitoh
Hideo
H
Matsuno
Yoshihiro
Y
Furuta
Koh
K
Tamura
Tomohide
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000737:chemistry / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004252:DNA Mutational Analysis / Q000379:methods*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007930:Leucine / Q000737:chemistry / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D001120:Arginine; D066246:ErbB Receptors; D007930:Leucine; D000077156:Gefitinib