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P3-088: Serum E-cadherin does not associate with response to gefitinib in patients with non-small cell lung cancer (NSCLC)

2007; Elsevier BV; Volume: 2; Issue: 8 Linguagem: Inglês

10.1097/01.jto.0000284064.64727.66

1556-1380

Anna Spreafico, Vanesa Gregorc, Rafał Dziadziuszko, Mariagrazia Viganò, Monica Giovannini, Mark W. Duncan, Paul A. Bunn, Eugenio Villa, Fred R. Hirsch,

Colorectal Cancer Treatments and Studies

The epidermal growth factor receptor (EGFR) is expressed in many human epithelial malignancies, including NSCLC. The response rates to EGFR tyrosine kinase inhibitors (TKIs) in unselected NSCLC patients rages from 9-27%. NSCLC cell lines highly sensitive to EGFR TKIs express E-cadherin. Patients with high E-cadherin expression in tumors samples have improved time-to-progression (TTP) after treatment with EGFR TKI erlotinib, indicating the significant role of epithelial-mesenchymal transition (EMT) to predict sensitivity/resistance to EGFR inhibitors. These results suggest that high E-cadherin expression would be a clinically relevant biomarker for patient’s selection to EGFR TKI therapy. The aim of the present study was to investigate the potential association between serum E-cadherin expression and clinical activity of gefitinib in European NSCLC patients. Serum E-cadherin levels were evaluated by ELISA using commercially available kit (R&D Systems). Statistical evaluation was performed by Kaplan-Meier analysis and a Cox proportional hazard model. Among 135 consecutive patients treated with gefitinib (median age, 67 years; 75% males; 83% ever smokers), 123 were evaluable for response, TTP and overall survival (OS). Forty-four (36%) had stable disease (SD) and 15 (13%) had objective response (OR). Serum E-cadherin levels ranged from 15 to 203 ng/mL with a median value of 30 ng/mL. The whole population was divided into two groups based on median E-cadherin levels (< 30 versus ≥ 30 ng/mL). Higher serum E-cadherin level was observed in patients with older age (P=.003), ECOG PS of 2 versus 0 or 1 (P=.027), and squamous cell histology (P=.045). The response rates were 13% and 11% in patients with low and high E-cadherin level, respectively (P=.809); disease control rates were 52% and 44% respectively (P=.415). Median TTP and OS were 3.5 and 5.8 months, and 3 and 7 months, in patients with low and high E-cadherin levels (P=.245; P=.434 respectively). These results indicate that higher E-cadherin levels are associated with age, advanced PS and squamous cell histology. Serum E-cadherin does not appear to predict response, TTP, and OS in patients with NSCLC after therapy with gefitinib. Corresponding E-cadherin tissue studies are ongoing.