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. 2017 Dec;14(6):7589-7596.
doi: 10.3892/ol.2017.7125. Epub 2017 Oct 3.

Impact of metastatic status on the prognosis of EGFR mutation-positive non-small cell lung cancer patients treated with first-generation EGFR-tyrosine kinase inhibitors

Yoshihiko Taniguchi  1 , Akihiro Tamiya  1 , Kenji Nakahama  1 , Yoko Naoki  1 , Masaki Kanazu  2 , Naoki Omachi  1 , Kyoichi Okishio  3 , Takahiko Kasai  4 , Shinji Atagi  3
Affiliations

Impact of metastatic status on the prognosis of EGFR mutation-positive non-small cell lung cancer patients treated with first-generation EGFR-tyrosine kinase inhibitors

Yoshihiko Taniguchi et al. Oncol Lett. 2017 Dec.

Abstract

The aim of the present study was to analyze the impact of metastatic status on the prognosis of epithelial growth factor receptor (EGFR) mutation-positive patients with non-small cell lung cancer (NSCLC) treated with first-generation EGFR-tyrosine kinase inhibitors (TKIs). A total of 178 EGFR mutation-positive patients with stage IIIB-IV and relapsed NSCLC who were treated with gefitinib or erlotinib as the first-line treatment were enrolled in the present study. Metastatic status, progression-free survival (PFS), overall survival (OS) and treatment-response rates were investigated. The association between the number of metastatic organ sites and patient prognosis was also investigated. The median age at the time of treatment was 72 (range, 39-91) years. A total of 168 patients had adenocarcinoma; 156 were treated with gefitinib. Patients with brain metastases, bone metastases, liver metastases and pleural effusion exhibited a significantly reduced PFS and OS time in the univariate analysis, compared with patients without each of these symptoms. In the multivariate analysis, bone metastasis was associated with a poorer PFS (hazard ratio, 2.11; 95% confidence interval, 1.44-3.09; P<0.001) and brain metastasis was associated with a poorer OS (hazard ratio, 2.41; 95% confidence interval, 1.46-3.95; P<0.001). No association was observed between metastatic status and treatment response rates. Higher numbers of different sites of organ metastases were associated with significantly poorer PFS and OS. Bone, brain metastasis and higher numbers of metastatic organ sites are negative prognostic factors for EGFR mutation-positive NSCLC patients treated with first-generation EGFR-TKIs.

Keywords: bone metastasis; brain metastasis; epithelial growth factor receptor; lung cancer; prognosis; tyrosine kinase inhibitors.

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Figures

Figure 1.
Figure 1.
Study flowchart. From 533 EGFR mutation-positive patients with NSCLC, 178 patients treated with GEF or ERL were enrolled in the present study. A total of 65 patients had brain metastases, 78 patients had bone metastases, 17 patients had liver metastases and 56 patients had pleural effusion at the time of first-line treatment. EGFR, epithelial growth factor receptor; NSCLC, non-small cell lung cancer; GEF, gefitinib; ERL, erlotinib; RT, radiotherapy; CT, chemotherapy; BEV, bevacizumab; AFA, afatinib; CRT, chemoradiotherapy; BSC, best supportive care.
Figure 2.
Figure 2.
Survival analysis of 178 non-small cell lung carcinoma patients with epithelial growth factor receptor mutations treated with first-generation tyrosine kinase inhibitors. PFS of patients with or without (A) brain metastasis, (B) bone metastasis, (C) liver metastasis and (D) PE. OS of patients with or without (E) brain metastasis, (F) bone metastasis, (G) liver metastasis and (H) PE. (I) PFS and (J) of patients stratified by the number of metastases at these sites (0, 1 or ≥2). *P<0.05 between groups. PFS, progression-free survival; PE, pleural effusion; OS, overall survival.
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