Abstract
Purpose: Two large, randomized, placebo-controlled trials (IRESSA NSCLC Trial Assessing Combination Therapy; INTACT 1 and 2) in non-small-cell lung cancer (NSCLC) failed to show survival benefit for gefitinib (IRESSA) in combination with first-line platinum-based chemotherapy. Epidermal growth factor receptor (EGFR) staining was assessed retrospectively in relation to survival response to gefitinib in combination with chemotherapy. Methods: Tumor biopsies obtained prior to start of therapy were assessed by immunohistochemistry for EGFR using the Dako EGFR pharmDx assay™ (Dako, Denmark). Analyses were stratified by trial and performed independently for patients randomized to placebo and gefitinib as well as for both treatment groups combined. A restricted backwards elimination Cox regression analysis was conducted to identify independent EGFR factors that were statistically significant (P < 0.10), and these were also tested for treatment interaction to assess if they served as predictive factors. Results: Analyses found two statistically significant EGFR-based prognostic factors representing growth pattern and percent membrane staining in patients treated with gefitinib (P = 0.0023), placebo (P = 0.0128), and both combined (P < 0.0001). The prognostic effect was independent of other known prognostic factors. There was no predictive effect of either the growth pattern or membrane staining variable. Conclusions: While some previous studies indicate that higher EGFR expression correlates with poor survival, our analyses provide statistically significant evidence that the combination of EGFR expression and growth pattern is a strong prognostic indicator for improved survival within this setting. The effects of membrane staining and growth pattern are still significant when adjusting for mutation.
Original language | English (US) |
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Pages (from-to) | 467-476 |
Number of pages | 10 |
Journal | Journal of Cancer Research and Clinical Oncology |
Volume | 135 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2009 |
Keywords
- Biomarkers
- Chemotherapy
- EGFR
- Gefitinib
- Immunohistochemistry
- NSCLC
- Tumor biopsies
ASJC Scopus subject areas
- Oncology
- Cancer Research