EGFR mutation: Significance as a stratification factor in the era of molecular-targeted therapy

Kim,Young   Hak; Masago,Katsuhiro; Togashi,Yosuke; Sakamori,Yuichi; Okuda,Chiyuki; Mio,Tadashi; Mishima,Michiaki

doi:10.3892/ol.2011.240

EGFR mutation: Significance as a stratification factor in the era of molecular-targeted therapy

Authors:
- Young Hak Kim
- Katsuhiro Masago
- Yosuke Togashi
- Yuichi Sakamori
- Chiyuki Okuda
- Tadashi Mio
- Michiaki Mishima
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Affiliations: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
Published online on: January 20, 2011 https://doi.org/10.3892/ol.2011.240
Pages: 383-387

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Abstract

Somatic mutations of epidermal growth factor receptor (EGFR) are the strongest predictive markers for the response to EGFR-tyrosine kinase inhibitors (TKIs). Patients with EGFR mutations generally receive EGFR-TKI treatment, and their survival has been significantly improved compared with that before the development of EGFR-TKIs. This study aimed to clarify the impact of EGFR mutational status on the survival of patients with non-small cell lung cancer (NSCLC) receiving cytotoxic agents, but not EGFR-TKIs, as their first-line chemotherapy. In addition, we analyzed patients with EGFR mutations to determine whether the timing of EGFR-TKI administration affects overall survival (OS). A total of 83 NSCLC patients with stage IIIB/IV who received chemotherapy alone and whose EGFR mutational status was known were investigated. Univariate and multivariate analysis for OS was performed using parameters such as age, gender, performance status (PS), histology, disease stage, smoking status, EGFR mutational status and administration of a first‑line regimen. Among the 52 patients with EGFR mutations who received EGFR-TKIs, OS between those who received EGFR‑TKIs as their first-line treatment and after chemotherapy were similar. Among the 83 patients who received cytotoxic agents as their first-line chemotherapy, the multivariate analysis showed OS to be significantly associated with PS (p<0.001), histology (p=0.039) and EGFR mutational status (p=0.040). OS was almost similar among the 52 patients with EGFR mutations who received EGFR-TKIs in a first- and second-line setting (25.6 vs. 26.8 months, p=0.914). The EGFR mutational status had a significant impact on the survival of NSCLC patients, although these patients did not receive EGFR-TKIs as their first-line chemotherapy. In future randomized trials, even when EGFR-TKIs are not included in experimental regimens, patients may need to be stratified by EGFR mutational status in order that study results be evaluated appropriately.

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