Impact of HER2 and EGFR gene status on gefitinib-treated patients with nonsmall-cell lung cancer.
We previously examined the relationship between epidermal growth factor receptor (EGFR) status and clinical outcomes of nonsmall-cell lung cancer (NSCLC) patients treated with gefitinib. In our study, we additionally examined HER2 status and investigate the impact of genetic status as predictors in Japanese NSCLC patients treated with gefitinib. The HER2 copy number status was determined by fluorescence in situ hybridization assay and mutation of HER2 exon 20 was determined by direct sequencing in 74 patients to investigate the relationship between molecular statuses including HER2 and EGFR and the clinical outcomes of patients treated with gefitinib. The high HER2 copy number was identified in 32 (43.2%) of 74 NSCLC patients and no HER2 exon 20 mutations were found. The high HER2 copy number was significantly associated with the sensitivity to gefitinib (p = 0.0045) and a prolonged progression-free survival (PFS) (p = 0.0089) in a univariate analysis, but not in a multivariate analysis. Multivariate analyses exhibited that the drug-sensitive EGFR mutation was an independent predictive factor of a better sensitivity to gefitinib (OR = 41.9, p = 0.002), prolonged overall survival (HR = 0.32, p = 0.019) and PFS (HR = 0.31, p = 0.0045). The high EGFR copy number might have a weak association with better response and prognosis without statistical significance. In conclusion, the drug-sensitive EGFR mutation, rather than HER2 and EGFR copy numbers, is a determinant of favorable clinical outcomes in gefitinib-treated patients with NSCLC, although the high HER2 copy number, to some extent, may influence the gefitinib effect.
Soh
Junichi
J
Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Toyooka
Shinichi
S
Ichihara
Shuji
S
Fujiwara
Yoshiro
Y
Hotta
Katsuyuki
K
Suehisa
Hiroshi
H
Kobayashi
Naruyuki
N
Ichimura
Kouichi
K
Aoe
Keisuke
K
Aoe
Motoi
M
Kiura
Katsuyuki
K
Date
Hiroshi
H
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D018734:Genes, erbB-2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib