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Journal of Cancer Research and Clinical Oncology

, Volume 139, Issue 10, pp 1691–1700 | Cite as

Solid predominant histology predicts EGFR tyrosine kinase inhibitor response in patients with EGFR mutation-positive lung adenocarcinoma

  • Tatsuya Yoshida
  • Genichiro IshiiEmail author
  • Koichi Goto
  • Kiyotaka Yoh
  • Seiji Niho
  • Shigeki Umemura
  • Shingo Matsumoto
  • Hironobu Ohmatsu
  • Kanji Nagai
  • Yuichiro Ohe
  • Atsushi OchiaiEmail author
Original Paper

Abstract

Background

The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) differs in patients with lung adenocarcinoma harboring EGFR-activating mutations. Although lung adenocarcinoma with EGFR-activating mutations has heterogeneous morphologic features, the predictive role of histologic subtype of lung adenocarcinoma with regard to the effectiveness of EGFR-TKIs in patients with EGFR-activating mutations has not been well defined.

Methods

Among 134 postoperative recurrence patients with lung adenocarcinoma harboring EGFR-activating mutation (L858R or exon 19 deletion) treated with EGFR-TKIs, we retrospectively analyzed 61 patients treated with EGFR-TKIs as first-line chemotherapy. All the tumors were classified according to the new histologic classification proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) into the following subtypes: lepidic, papillary, acinar, micropapillary, or solid predominant subtype. We evaluated the correlation between the histologic subtype and the clinical efficacy of EGFR-TKIs.

Results

In overall response rate, adenocarcinoma with solid predominant subtype is significantly worse than with non-solid predominant subtype (61 vs. 88 %, P = 0.03). The median progression-free survival (PFS) and overall survival after EGFR-TKI treatment were significantly shorter for the patients with solid predominant subtype than for those with non-solid predominant subtype (median PFS of 7.7 vs. 13.5 months, P = 0.002, and median OS of 21.5 vs. 31.0 months, P = 0.028).

Conclusions

This study indicated that among patients with lung adenocarcinoma harboring activating EGFR mutations treated with EGFR-TKIs, solid predominant subtype according to IASLC/ATS/ERS classification is a response predictor for EGFR-TKI.

Keywords

Lung adenocarcinoma Epidermal growth factor receptor mutation Epidermal growth factor receptor tyrosine kinase inhibitor Solid predominant subtype 

Abbreviations

EGFR

Epidermal growth factor receptor

TKI

Tyrosine kinase inhibitor

NSCLC

Non-small cell lung cancer

PFS

Progression-free survival

IASLC

International Association for the Study of Lung Cancer

ATS

American Thoracic Society

ERS

European Respiratory Society

RECIST

Response evaluation criteria solid tumor criteria

ORR

Objective response rate

OS

Overall survival

HR

Hazard ratio

CI

Confidence interval

HGF

Hepatocyte growth factor

Notes

Acknowledgments

This work was supported by National Cancer Center Research and Development Fund (23-A-12 and 23-K-18), the Foundation for the Promotion of Cancer Research, 3rd-Term Comprehensive 10-Year Strategy for Cancer Control, Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation, and JSPS KAKENHI (24659185).

Conflict of interest

All authors declare no conflicts of interest.

Supplementary material

432_2013_1495_MOESM1_ESM.doc (42 kb)
Supplementary material 1 (DOC 42 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Tatsuya Yoshida
    • 1
    • 2
  • Genichiro Ishii
    • 1
    Email author
  • Koichi Goto
    • 2
  • Kiyotaka Yoh
    • 2
  • Seiji Niho
    • 2
  • Shigeki Umemura
    • 2
  • Shingo Matsumoto
    • 2
  • Hironobu Ohmatsu
    • 2
  • Kanji Nagai
    • 2
  • Yuichiro Ohe
    • 2
  • Atsushi Ochiai
    • 1
    Email author
  1. 1.Division of Pathology, Research Center for Innovative OncologyNational Cancer Center Hospital EastKashiwaJapan
  2. 2.Division of Thoracic OncologyNational Cancer Center Hospital EastKashiwaJapan

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