Epidermal growth factor receptor expression analysis in chemotherapy-naive patients with advanced non-small-cell lung cancer treated with gefitinib or placebo in combination with platinum-based chemotherapy

Giuseppe Giaccone, Renee B. Iacona, Abderrahim Fandi, Mette Janas, Judith S. Ochs, Roy S. Herbst, David H. Johnson

Research output: Contribution to journalArticle

8 Scopus citations

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 languageEnglish (US)
Pages (from-to)467-476
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume135
Issue number3
DOIs
StatePublished - Mar 1 2009

Keywords

  • Biomarkers
  • Chemotherapy
  • EGFR
  • Gefitinib
  • Immunohistochemistry
  • NSCLC
  • Tumor biopsies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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