Impact of HER2 and EGFR gene status on gefitinib-treated patients with nonsmall-cell lung cancer

Junichi Sou, Shinichi Toyooka, Shuji Ichihara, Yoshiro Fujiwara, Katsuyuki Hotta, Hiroshi Suehisa, Naruyuki Kobayashi, Kouichi Ichimura, Keisuke Aoe, Motoi Aoe, Katsuyuki Kiura, Hiroshi Date

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1162-1167
Number of pages6
JournalInternational Journal of Cancer
Volume121
Issue number5
DOIs
Publication statusPublished - Sep 1 2007

Fingerprint

erbB-1 Genes
Non-Small Cell Lung Carcinoma
Epidermal Growth Factor Receptor
Mutation
Disease-Free Survival
Exons
Multivariate Analysis
gefitinib
Fluorescence In Situ Hybridization
Pharmaceutical Preparations
Survival

Keywords

  • Amplification
  • EGFR
  • Gefitinib
  • HER2
  • Mutation
  • NSCLC

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Impact of HER2 and EGFR gene status on gefitinib-treated patients with nonsmall-cell lung cancer. / Sou, Junichi; Toyooka, Shinichi; Ichihara, Shuji; Fujiwara, Yoshiro; Hotta, Katsuyuki; Suehisa, Hiroshi; Kobayashi, Naruyuki; Ichimura, Kouichi; Aoe, Keisuke; Aoe, Motoi; Kiura, Katsuyuki; Date, Hiroshi.

In: International Journal of Cancer, Vol. 121, No. 5, 01.09.2007, p. 1162-1167.

Research output: Contribution to journalArticle

Sou, J, Toyooka, S, Ichihara, S, Fujiwara, Y, Hotta, K, Suehisa, H, Kobayashi, N, Ichimura, K, Aoe, K, Aoe, M, Kiura, K & Date, H 2007, 'Impact of HER2 and EGFR gene status on gefitinib-treated patients with nonsmall-cell lung cancer', International Journal of Cancer, vol. 121, no. 5, pp. 1162-1167. https://doi.org/10.1002/ijc.22818
Sou, Junichi ; Toyooka, Shinichi ; Ichihara, Shuji ; Fujiwara, Yoshiro ; Hotta, Katsuyuki ; Suehisa, Hiroshi ; Kobayashi, Naruyuki ; Ichimura, Kouichi ; Aoe, Keisuke ; Aoe, Motoi ; Kiura, Katsuyuki ; Date, Hiroshi. / Impact of HER2 and EGFR gene status on gefitinib-treated patients with nonsmall-cell lung cancer. In: International Journal of Cancer. 2007 ; Vol. 121, No. 5. pp. 1162-1167.
@article{29faa13685c740bc9612c5bbed0e2b33,
title = "Impact of HER2 and EGFR gene status on gefitinib-treated patients with nonsmall-cell lung cancer",
abstract = "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.",
keywords = "Amplification, EGFR, Gefitinib, HER2, Mutation, NSCLC",
author = "Junichi Sou and Shinichi Toyooka and Shuji Ichihara and Yoshiro Fujiwara and Katsuyuki Hotta and Hiroshi Suehisa and Naruyuki Kobayashi and Kouichi Ichimura and Keisuke Aoe and Motoi Aoe and Katsuyuki Kiura and Hiroshi Date",
year = "2007",
month = "9",
day = "1",
doi = "10.1002/ijc.22818",
language = "English",
volume = "121",
pages = "1162--1167",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Impact of HER2 and EGFR gene status on gefitinib-treated patients with nonsmall-cell lung cancer

AU - Sou, Junichi

AU - Toyooka, Shinichi

AU - Ichihara, Shuji

AU - Fujiwara, Yoshiro

AU - Hotta, Katsuyuki

AU - Suehisa, Hiroshi

AU - Kobayashi, Naruyuki

AU - Ichimura, Kouichi

AU - Aoe, Keisuke

AU - Aoe, Motoi

AU - Kiura, Katsuyuki

AU - Date, Hiroshi

PY - 2007/9/1

Y1 - 2007/9/1

N2 - 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.

AB - 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.

KW - Amplification

KW - EGFR

KW - Gefitinib

KW - HER2

KW - Mutation

KW - NSCLC

UR - http://www.scopus.com/inward/record.url?scp=34547098367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547098367&partnerID=8YFLogxK

U2 - 10.1002/ijc.22818

DO - 10.1002/ijc.22818

M3 - Article

C2 - 17487844

AN - SCOPUS:34547098367

VL - 121

SP - 1162

EP - 1167

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 5

ER -