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Published on: August 11, 2017
Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib ('Iressa',
H S Parra1, R Cavina, F Latteri
1Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Via A Manzoni 56, Rozzano, Milan 20089, Italy. sotolatteri@hotmail.com
Abstract:
Gefitinib ('Iressa', ZD1839) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated antitumour activity and favourable tolerability in Phase II studies. We investigated whether EGFR expression levels could predict for response to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC), who received gefitinib (250 mg day(-1)) as part of a worldwide compassionate-use programme. Tissue samples were analysed by immunohistochemistry to assess membrane EGFR immunoreactivity. Of 147 patients enrolled in our institution, 50 patients were evaluable for assessment of both clinical response and EGFR expression. The objective tumour response rate was 10% and disease control was achieved in 50% of patients. Although high EGFR expression was more common in squamous-cell carcinomas than adenocarcinomas, all objective responses were observed in patients with adenocarcinoma. Response and disease control with gefitinib were not associated with high EGFR expression. Overall, median survival was 4 months, and the 1-year survival rate was 18%. Strong EGFR staining correlated with shorter survival time for all patients. Gefitinib demonstrated promising clinical activity in this group of patients with NSCLC. These results have also shown that EGFR expression is not a significant predictive factor for response to gefitinib.
Insights
Gefitinib shows promise for advanced non-small-cell lung cancer (NSCLC). However, epidermal growth factor receptor (EGFR) levels do not predict treatment response, and high EGFR expression correlated with shorter survival.
Area of Science:
- Oncology
- Pharmacology
Background:
- Gefitinib (Iressa) is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with demonstrated antitumor activity.
- Previous studies indicated favorable tolerability and efficacy in Phase II trials for advanced non-small-cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate if epidermal growth factor receptor (EGFR) expression levels could predict patient response to gefitinib in advanced non-small-cell lung cancer (NSCLC).
Main Methods:
- 147 patients with advanced NSCLC received gefitinib (250 mg/day) under a compassionate-use program.
- Tissue samples were analyzed using immunohistochemistry to assess membrane EGFR immunoreactivity.
- Clinical response and EGFR expression were evaluated in 50 evaluable patients.
Main Results:
- The objective tumor response rate was 10%, with disease control achieved in 50% of patients.
- All objective responses occurred in patients with adenocarcinoma, irrespective of EGFR expression levels.
- Strong EGFR staining was associated with shorter survival times across all patients.
Conclusions:
- Gefitinib demonstrated promising clinical activity in patients with advanced NSCLC.
- EGFR expression levels were not found to be a significant predictive factor for response to gefitinib.
- High EGFR expression correlated with poorer survival outcomes in this NSCLC cohort.
