Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence.
OBJECTIVE
To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection.


METHODS
We sequenced exons 18-21 of the EGFR gene using total RNA extracted from 59 patients with lung cancer who were treated with gefitinib for recurrent lung cancer. Gefitinib effectiveness was evaluated by both imaging studies and change in serum carcinoembryonic antigen (CEA) levels.


RESULTS
EGFR mutations were found in 33 patients (56%). Of these mutations, 17 were deletions around codons 746-750 and 15 were point mutations (12 at codon 858, three at other codons), and one was an insertion. EGFR mutations were significantly more prevalent in females, adenocarcinoma, and never-smokers. Gefitinib treatment resulted in tumor shrinkage and/or CEA decrease to less than half of the baseline level in 26 patients, tumor growth and/or CEA elevation in 24 patients, and gefitinib effect was not assessable in nine patients. Female, never-smoking patients with adenocarcinoma tended to respond better to gefitinib treatment. Gefitinib was effective in 24 of 29 patients with EGFR mutations, compared with two of 21 patients without mutations (P < .0001). Of note, del746-750 might be superior to L858R mutations for prediction of gefitinib response. Patients with EGFR mutations survived for a longer period than those without the mutations after initiation of gefitinib treatment (P = .0053).


CONCLUSIONS
EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting.
Mitsudomi
Tetsuya
T
Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. mitsudom@aichi-cc.jp
Kosaka
Takayuki
T
Endoh
Hideki
H
Horio
Yoshitsugu
Y
Hida
Toyoaki
T
Mori
Shoichi
S
Hatooka
Shunzo
S
Shinoda
Masayuki
M
Takahashi
Takashi
T
Yatabe
Yasushi
Y
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000502:physiology*; D005091:Exons; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D017354:Point Mutation; D011237:Predictive Value of Tests; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012737:Sex Factors; D016019:Survival Analysis
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D012313:RNA; D066246:ErbB Receptors; D000077156:Gefitinib