Background: In patients with non-small cell lung cancer (NSCLC), a higher response rate can be achieved with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) when selection for therapy is guided by mutation analysis or gene amplification. However, both tests are complex and require tumour tissue. Simple methods to identify responders prior to EGFR-TKI treatment are urgently needed. This study aimed to define the relation between serum sEGFR levels, carcinoembryonic antigen (CEA) and survival in NSCLC patients treated with EGFR-TKIs.

Methods: Patients with stage III/IV NSCLC treated with gefitinib or erlotinib between July 2002 and December 2005 were reviewed. Levels of serum soluble EGFR (sEGFR) were determined by a sandwich quantitative enzyme-linked immunosorbent assay. A chemiluminescence immunoassay was used for CEA. The relation between sEGFR and survival was investigated.

Results: One hundred and two NSCLC patients, mainly stage IV (80%), were identified. Mean sEGFR at baseline was 55.9 μg/l (range 35.3–74.5 μg/l). The median CEA level was 11.1 μg/l (range <1.0–2938.0 μg/l). Median overall survival was 5.2 months (range 1–52 months). Decreasing log CEA values (HR 1.51, 95% CI 1.11–2.04, multivariate analysis) and increasing sEGFR values (HR 0.96, 95% CI 0.93–0.99, multivariate analysis) were both independently associated with prolonged survival. Higher levels of pre-treatment sEGFR were associated with lower risk of progressive disease within three months (p=0.04).

Conclusions: Both baseline sEGFR and CEA levels in NSCLC patients receiving EGFR-TKIs showed a significant correlation with survival. To distinguish whether these factors have a predictive or a prognostic value, validation is warranted in an independent patient series containing a control arm without EGFR-TKI treatment.