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

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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.

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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

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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.

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Authors and Affiliations

  1. Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Tatsuya Yoshida, Genichiro Ishii & Atsushi Ochiai

  2. Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan

    Tatsuya Yoshida, Koichi Goto, Kiyotaka Yoh, Seiji Niho, Shigeki Umemura, Shingo Matsumoto, Hironobu Ohmatsu, Kanji Nagai & Yuichiro Ohe

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  1. Tatsuya Yoshida
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  2. Genichiro Ishii
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  3. Koichi Goto
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  4. Kiyotaka Yoh
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  11. Atsushi Ochiai
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Correspondence to Genichiro Ishii or Atsushi Ochiai.

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Yoshida, T., Ishii, G., Goto, K. et al. Solid predominant histology predicts EGFR tyrosine kinase inhibitor response in patients with EGFR mutation-positive lung adenocarcinoma. J Cancer Res Clin Oncol 139, 1691–1700 (2013). https://doi.org/10.1007/s00432-013-1495-0

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