Evaluation of epidermal growth factor receptor (EGFR) as a predictive marker in patients with non-small-cell lung cancer (NSCLC) receiving first-line gefitinib combined with platinum-based chemotherapy
2004; Lippincott Williams & Wilkins; Volume: 22; Issue: 14_suppl Linguagem: Inglês
10.1200/jco.2004.22.14_suppl.7013
ISSN1527-7755
AutoresLisa Bailey, M. Janas, Karsten Schmidt, Niels Bindslev, Michael Wolf, John Grous, Jon Askaa, Roy S. Herbst, David H. Johnson, Giuseppe Giaccone,
Tópico(s)Lung Cancer Diagnosis and Treatment
Resumo7013 Background: In two Phase III trials (INTACT 1 & 2), gefitinib (‘Iressa’, ZD1839) in combination with first-line platinum-based chemotherapy regimens failed to show benefit in terms of survival when compared with chemotherapy alone in patients (pts) with NSCLC. The primary objective of this analysis was to evaluate if EGFR staining was predictive of survival. Methods: Pretreatment tumor biopsies were assessed by immunohistochemistry for EGFR using the DakoCytomation pharmDx assay™. The percentage of tumor cells was assessed using 4 levels of intensity: no staining, 0; weak, 1+; moderate, 2+; strong, 3+; as well as the presence of complete membrane staining. 516 pts (INTACT 1/2, 219/297) with tumor samples fully evaluable for EGFR were analyzed in the per protocol population of the combined trials. The analysis was stratified by trial and performed independently for pts randomized to placebo or gefitinib. A restricted backwards elimination Cox regression analysis was conducted to identify independent EGFR factors. Variables found to be significant (p<0.1) were also tested for treatment interaction to determine if they served as predictive factors. Results: The demographics of the analysis population were representative of the overall population in each trial as were common disease characteristics. The analysis showed that two EGFR-based variables are independent strong prognostic factors for both placebo- and gefitinib-treated patients. However, no interactions with treatment (ie no value for predicting benefit of gefitinib treatment) were indicated for either of these two variables (p=0.8688 and 0.4967) or for any other EGFR-based variables. Conclusion: Given the overall trial results for INTACT 1 & 2 showing no survival benefit between gefitinib and placebo, it was highly unlikely that EGFR variables would identify a subset of pts who receive survival benefit. The data presented support this hypothesis. 'Iressa' is a trademark of the AstraZeneca group of companies 'PharmDx assay' is a trademark of DakoCytomation Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Pharmaceuticals; DakoCytomation AstraZeneca; DakoCytomation; Genentech AstraZeneca AstraZeneca AstraZeneca Pharmaceuticals
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